Systems and methods for coordinating musculoskeletal and cardiovascular or cerebrovascular hemodynamics

ABSTRACT

Described herein are methods for determining a target musculoskeletal activity cycle (MSKC) to cardiac cycle (CC) timing relationship. The method may include detecting a first characteristic of a signal responsive to a CC timing of a user that repeats at a frequency that corresponds to a heart rate of the user; detecting a second characteristic of a signal responsive to a rhythmic musculoskeletal cycle activity (MSKC) timing of the user that repeats at a frequency that corresponds to the MSKC rate of the user; determining a value representative of an actual timing relationship between the first characteristic and the second characteristic; detecting a third characteristic of a signal corresponding to a physiological metric that varies with the actual timing relationship between the first and second characteristics; and determining a target value representative of a preferred timing relationship between the first and second characteristics.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/553,732, titled “Systems and Methods for Coordinating Musculoskeletaland Cardiovascular or Cerebrovascular Hemodynamics”, filed Nov. 25,2014, which is a continuation-in-part to co-pending U.S. patentapplication Ser. No. 13/589,073, titled “System and Method for ReliablyCoordinating Musculoskeletal and Cardiovascular Hemodynamics”, filed onAug. 17, 2012, and which claims priority to U.S. provisional patentapplication Ser. No. 61/525,689, titled “System and Method forSelectively Coordinating User Movement and Muscle Contraction with UserCardiac Pumping Cycle”, filed on Aug. 19, 2011, each of which is hereinincorporated by reference in its entirety. This application is alsorelated to U.S. patent application Ser. No. 14/216,960, titled“Coordinating Musculoskeletal and Cardiovascular Hemodynamics”, filed onMar. 17, 2014, which claims priority to U.S. provisional patentapplication Ser. No. 61/798,799, titled “Systems and Methods forReliably Coordinating Musculoskeletal and Cardiovascular Hemodynamics”,filed on Mar. 15, 2013, both of which are herein incorporated byreference in their entirety. This application is related to U.S.provisional patent application Ser. No. 62/056,730, titled “CoordinatingMusculoskeletal and Cardiovascular Hemodynamics”, filed on Sep. 29,2014, which is herein incorporated by reference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety, as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference in its entirety.

COPYRIGHT NOTICE

A portion of the disclosure of this patent document contains materialthat is subject to copyright protection. The copyright owner has noobjection to the facsimile reproduction by anyone of the patent documentor the patent disclosure as it appears in the Patent and TrademarkOffice patent file or records, but otherwise reserves all copyrightrights whatsoever.

TECHNICAL FIELD

This invention relates generally to the field of human physiology, andmore specifically to new and useful methods, apparatuses, systems andcomputer program products for coordinating musculoskeletal andcardiovascular or cerebrovascular hemodynamics.

BACKGROUND

Blood is circulated through the body by the heart during its rhythmicpumping cycle, which consists of two distinct periods—systole anddiastole. Heart muscle contracts to eject blood from the ventriclesduring the systolic period of each cardiac cycle (CC). Ejection of bloodfrom the ventricles generates arterial blood pressure and flow adequateto deliver blood throughout the body. The blood transports oxygen,nutrients and metabolic products, removes carbon dioxide and waste, andfacilitates critical physiological functions such as heat exchange. Theheart subsequently relaxes during the diastolic period of the CC, whenthe atrial and ventricular chambers refill with blood in preparation forthe heart's next contraction.

Unlike the rest of the body, which receives most of its blood flowduring the systolic portion of the arterial pressure cycle, contractionof the heart during systole generates high forces within the heart'smuscular walls, preventing blood from flowing through the heart muscleitself at that time. Therefore, the heart's own arterial blood supply isdelivered primarily during diastole, when the heart muscle is relaxingand the heart chambers are filling for the next contraction, while atthe same time the lower residual blood pressure in the aorta pushesblood through the coronary arteries and into the myocardial muscle tosupply the heart with its needed oxygen and nutrients.

In addition to the heart's pumping function, the musculoskeletal (MSK)system also pumps arterial and venous blood throughout the body duringphysical activity in a couple of important ways. First, skeletal musclecontraction and relaxation cycles during rhythmic physical activitiescause regular oscillations in peripheral arterial and venous bloodpressure or flow due to intermittent compression of the vasculature thattravels within, between, and adjacent to the skeletal muscles. Second,MSK movement can lead to periodic acceleration and deceleration of theintravascular volume of blood against gravity and inertia.

When rhythmic muscle contractions and MSK movements are favorablycoordinated with the timing of the heart's pump cycle, the MSK andcardiac pumping systems can augment one another to increase blood flowto and perfusion of important areas of the body with less pumping energyexpended by the heart. This favorable coordination of these two pumpingsystems can be referred to as “musculoskeletal counterpulsation” (MCP).During MCP, maximum rhythmic MSK-induced blood pumping consistentlyincreases central arterial blood pressure when the heart is relaxing andrefilling between contractions (i.e. during diastole), and the maximumcardiac induced pumping (systole) consistently occurs between MSKinduced maximal central arterial pressure events. On the other hand,when rhythmic muscle contractions and MSK movements occur withuncoordinated, or worse, unfavorably coordinated timing, blood flow andperfusion are decreased along with a concurrent decrease in pumpingefficiencies. Unfavorable coordination occurs, for example, when thecardiac and MSK systems consistently pump blood maximally into thecentral circulation at substantially the same time during rhythmicphysical activity. This unfavorable coordination of the two pumpingsystems can be referred to as “inverse musculoskeletal counterpulsation”(iMCP).

Typically, when individuals walk, run, bicycle, or participate in anyrhythmic physical activity, most experience favorable coordinationbetween MSK blood pumping and CC blood pumping only intermittently. Evenwhen an individual's heart rate (HR) and MSK activity cycle rate (MSKR)happen to be substantially equal, the respective timing of the twopumping systems may result in favorable or unfavorable coordination, orsomewhere in between. A certain degree of “cardio-locomotorsynchronization” can occur during rhythmic physical activity, in whichthe timing of an individual's MSK pump cycle relative to the heart'spump cycle tends, statistically, to naturally favor MCP. However, whensuch synchrony does occur, it is usually only a temporary phenomenonsince HR and/or MSKR can change as environmental factors vary (e.g.,running in hilly terrain or variable wind) or with any of severalphysical changes, such as alterations in effort, speed, hydration,temperature, catecholamine levels, or fatigue.

The benefits of favorable coordination between MSK movements and theheart's pump cycle can include improved perfusion and oxygenation ofcardiac and peripheral skeletal muscle and possibly other tissues;decreased HR due to increased cardiac preload and stroke volume;decreased systolic blood pressure and pulse pressure; decreased requiredrespiratory effort to meet decreased oxygen demands; and reduced musclefatigue due to improved skeletal muscle perfusion. These benefits canpotentially lead to increased physiological efficiency, decreasedmyocardial stress, increased aerobic energy production, improved aerobicfat metabolism, enhanced individual performance, and a potentialincrease in the health benefits and safety of rhythmic physicalactivity. Conversely, unfavorable coordination between MSK movements andthe heart's pump cycle can lead to the opposite of all of these effects.

Some of the general approaches that we have described for favorablycoordinating MSKC and CC timing during rhythmic physical activityinclude (1) the provision of adaptive real-time MSKC timing prompts to auser, (2) automated means of adjusting exercise equipment settings inorder to adaptively modify a user's MSKC timing; and (3) automated meansof adjusting artificial cardiac pacemaker systems to adaptively adjustthe timing of the CC relative to the MSKC of the user. Each of thesegeneral approaches may require the identification and use of sensedphysiological metrics to assist with identifying a target timingrelationship between the MSKC and CC of the user, measuringphysiological impacts of the timing relationship, and tracking progressin favorably influencing physiology over time.

The methods and systems described below are for guiding a user to obtainand maintain favorable coordination of MSKC and CC hemodynamics, andmore directly, to achieve or maintain system calibration, to increasethe accuracy of identifying, achieving, and maintaining target pumptiming relationships, and/or to track the effectiveness of achievingphysiological benefit during rhythmic physical activity.

SUMMARY

Described herein are methods for guiding a user to a target rhythmicmusculoskeletal cycle activity (MSKC) to cardiac cycle (CC) timingrelationship. In general, the methods may include detecting a firstsignal responsive to the timing of the CC of a user using a firstsensor; determining the heart rate (HR) of the user using at least aportion of the first signal detected by the first sensor using a firstprocessor, providing a recurrent prompt from a prompt device to the useras a timing indication for performance of a rhythmic musculoskeletalactivity; detecting a second signal responsive to the rhythmicmusculoskeletal activity timing of the user that repeats at an MSKR ofthe user using a second sensor; determining an actual MSKC to CC timingrelationship between the first signal and the second signal using thefirst processor, comparing the actual timing relationship of the firstsignal and the second signal to a target MSKC to CC timing relationship;and adjusting the timing indication of the recurrent prompt from theprompt device to the user based on a difference between the actualtiming relationship and the target timing relationship, so as to reducethe magnitude of the difference.

In some embodiments, the target timing relationship is provided by thefirst processor or a second processor. In some embodiments, the timingindication guides the user to a musculoskeletal activity cycle rate(MSKR). In some embodiments, the HR of the user is substantially aninteger multiple of the MSKR. In some embodiments, the recurrent promptrepeats at a prompt rate such that the HR is substantially an integermultiple of said prompt rate. In some embodiments, adjusting the timingindication of the recurrent prompt from the prompt device includesadjusting the prompt rate. In some embodiments, the recurrent prompt isan audible prompt that includes a beat of a musical track. In someembodiments, a volume of the beat of the musical track that includes therecurrent prompt is controlled separately from a volume of a rest of themusical track based on a user setup configuration, a program setupconfiguration, a consistency of the user in stepping to the recurrentprompt, and/or an accuracy of the user stepping at the timingindication. In some embodiments, the first sensor signal includes atleast one of an electrocardiogram (ECG) and a plethysmogram. In someembodiments, the second sensor includes an accelerometer, anelectromyographic sensor, a pressure sensor, a switch, a camera, agryroscope, a proximity sensor, and/or a plethysmographic sensor.

In some embodiments, detecting the first signal includes identifyinginstances of one or more features of the first signal that occur onceper CC. In some embodiments, the features correspond to one or more ofan ECG R-wave, an ECG T-wave, an end of the ECG T-wave, a peak of acardiovascular systolic pressure, a nadir of a diastolic cardiovascularpressure, and a transition point in a cardiovascular pressure of theuser. In some embodiments, the method further includes determining theMSKR of the user, using the first processor or the second processor,based on the second signal detected by the second sensor.

Described herein are methods for determining a target MSKC to CC timingrelationship. In general, the methods may include detecting a firstcharacteristic of a signal responsive to a CC timing of a user thatrepeats at a frequency that corresponds to a HR of the user using afirst sensor, detecting a second characteristic of a signal responsiveto a rhythmic MSKC timing of the user that repeats at a frequency thatcorresponds to the MSKR of the user using the first sensor or a secondsensor; determining a value representative of an actual timingrelationship between the first characteristic and the secondcharacteristic using a first processor, detecting a third characteristicof a signal using the first, the second, or a third sensor correspondingto a physiological metric that varies with the actual timingrelationship between the first and second characteristics; anddetermining a target value representative of a preferred timingrelationship between the first and second characteristics by identifyingthe value representative of the actual timing relationship thatcorresponds with a preferred value of the variable physiological metric,using the first processor or a second processor.

In some embodiments, the method further includes providing a recurrentprompt from a prompt device at a prompt rate to the user as a timingindication for performance of the rhythmic MSKC. In some embodiments,the prompt device is controlled by the first processor or the secondprocessor. Further, in some embodiments, the HR of the user issubstantially an integer multiple of the prompt rate. In someembodiments, the prompt rate is provided to guide the user to vary theMSKC timing relative to the CC timing. In some embodiments, the targetvalue representative of the preferred timing relationship is naturallyachieved by the user. In some embodiments, the prompt device prompts theuser to maintain the naturally achieved preferred timing relationship.In some embodiments, the prompt device is configured by the first orsecond processor to controllably guide the user to at least twodifferent actual timing relationships. In some embodiments, at least twoof the first, second, or third characteristics are aspects of a firstsignal from the first sensor. In some embodiments, the at least one ofthe first, second or third characteristics includes a Fourier transform.In some embodiments, the value representative of an actual timingrelationship is determined by using a cross correlation between thefirst characteristic from the first sensor and the second characteristicfrom the second sensor. In some embodiments, the first characteristicand the second characteristic are derived from independent first andsecond signals from the first and second sensors, respectively. In someembodiments, the physiological metric includes the HR, a tissue pH, atissue lactic acid level, a respiratory volume, a respiratory exchangeratio, an oxygen consumption, or a CO₂ production of the user.

In some embodiments, the method further includes prompting an adjustmentof the cadence of the user to guide the user towards the target relativetiming relationship. In some embodiments, the method further includesguiding the user to the HR and a MSKR, such that an absolute differencebetween the two rates is between 0.25 and 5 per minute. In someembodiments, the preferred value of the variable physiological metric isa most commonly occurring actual timing relationship. In someembodiments, the user achieves the target timing relationship withoutprompting when the HR and the MSKR are approximately equal. In someembodiments, the preferred value of the variable physiological metric isa most commonly occurring actual timing relationship. In someembodiments, the first sensor technology includes photoplethysmography,impedance plethysmography, laser-Doppler blood flow, acoustic sensing,or arterial tonometry. In some embodiments, the preferred value of thephysiological metric is a lowest average HR of the user.

Described herein are methods for favorably coordinating a timingrelationship between an MSKC of a rhythmic musculoskeletal activity of auser and a CC of the user. In general, the methods may includerepetitively detecting a signal responsive to cyclically-varyingarterial blood volume in a tissue of the user, using a sensor;determining a first measured characteristic of the signal that repeatsat a HR of the user and determining the HR of the user from the firstcharacteristic; recurrently providing a guidance prompt from a promptdevice to the user as a timing indication for performance of a rhythmicMSK activity, determining a value of a second measured characteristic ofthe signal that varies with an actual MSKC to CC timing relationship ofthe user; and adjusting the guidance based on a trend of the value ofthe second measured characteristic towards a relative preferred value ofthe second measured characteristic corresponding to a target MSKC to CCtiming relationship, thereby guiding the user towards substantiallyobtaining and maintaining the target MSKC to CC timing relationship. Insome embodiments, the HR is an integer multiple of the rate of thetiming indication.

Described herein are methods for favorably coordinating a timingrelationship between an MSKC of a rhythmic musculoskeletal activity of auser and a CC of the user. In general, the methods may includerecurrently providing a movement guidance from a prompt device to theuser for guiding performance of a rhythmic musculoskeletal activity;and, repetitively, detecting a signal, using a sensor, that correlatesto a cyclically-varying arterial blood volume in a tissue of the user;determining an actual value of a measured characteristic of the signalthat varies with the timing relationship between the MSKC and the CC ofthe user, using a processor, and computing a trend of the actual valueof the measured characteristic using a processor, and adjusting themovement guidance based on the trend of the actual value so as to causethe actual value of the measured characteristic to approach a relativepreferred value of the measured characteristic.

In some embodiments, the movement guidance includes at least one of arecurrent audible, visual, or tactile prompt. In some embodiments, thedetecting step includes using as the sensor technologyphotoplethysmography, impedance plethysmography, laser-Doppler bloodflow, acoustic sensing, or arterial tonometry. In some embodiments, themeasured characteristic of the signal that varies with the timingrelationship between the MSKC and the CC of the user includes at leastone of a pulse amplitude, a measure of relative peak to valley signalwaveform curvature, a measure of signal waveform peak curvature, ameasure of signal waveform valley curvature, a measure of signalwaveform complexity, and a measure of an asymmetry of the signalwaveform. In some embodiments, the relative preferred value of themeasured characteristic is a threshold crossing of an increasing trend,a threshold crossing of a decreasing trend, a local maximum, or a localminimum of the trend of the actual value of the measured characteristic.In some embodiments, a heart rate of the user is substantially aninteger multiple of the prompt rate.

In some embodiments, the method further includes detecting, using one ormore sensors, signals that correlate to a heart rate of the user and amusculoskeletal activity cycle rate (MSKR) of the user; determining,using the processor, the heart rate of the user and an MSKR of the userby processing the one or more signals; specifying a maximum allowableabsolute difference between the heart rate and the MSKR; and executing,using the processor, the above-mentioned steps of: recurrently providinga movement guidance from a prompt device to the user for guidingperformance of a rhythmic musculoskeletal activity; and, repetitively,detecting a signal, using a sensor, that correlates to acyclically-varying arterial blood volume in a tissue of the user,determining an actual value of a measured characteristic of the signalthat varies with the timing relationship between the MSKC and the CC ofthe user, using a processor, and computing a trend of the actual valueof the measured characteristic using a processor; and adjusting themovement guidance based on the trend of the actual value so as to causethe actual value of the measured characteristic to approach a relativepreferred value of the measured chaiacteristic, only when an absolutevalue of a difference between the MSKR and heart rate is less than, orless than or equal to, a specified allowable difference.

In some embodiments, the method further includes specifying a targetMSKR; and recurrently providing a prompt from the prompt device when theabsolute value of the difference between the MSKR and the target MSKR isgreater, or greater than or equal to, the specified allowabledifference, the prompt repeating at a prompt rate.

In some embodiments, the target MSKR is an integer multiple of theprompt rate. In some embodiments, the measured characteristic of thesignal is computed using a combination of two or more uniquecharacteristics of the signal that vary with the timing relationshipbetween the MSKC and the CC of the user. In some embodiments, the methodfurther includes detecting with the sensor a second signal thatcorrelates to the HR or the MSKR of the user. In some embodiments, themethod further includes detecting with a second sensor signals thatcorrelate to the HR or the MSKR of the user. In some embodiments, thetarget cadence equals a target heart rate of the user. In someembodiments, the movement guidance includes instructing the user in atleast one of an MSK activity timing and an MSK activity effort. In someembodiments, instructing the user in the MSK activity effort includesproviding movement guidance on stride length during running or walking,gear use while riding a bicycle, resistance, MSKC movement distance,incline using exercise equipment, or stroke length during rowing orswimming. In some embodiments, instructing the user in the MSK activitytiming includes providing an MSKC prompt at a prompt rate to guide theuser to an MSKR that is an integer multiple of the prompt rate.

In some embodiments, the method further includes a calibration process,said calibration process including detecting a second characteristic ofat least one of the signal and one or more additional signalscorresponding to a physiological metric that varies with the timingrelationship between the MSKC and the CC of the user, using the sensoror one or more additional sensors; and determining the relativepreferred value of the measured characteristic as a relative value ofthe trend that corresponds with a preferred value of the physiologicalmetric.

In some embodiments, the physiological metric includes a measure ofheart rate, minute ventilation, blood pressure, blood flow, cardiacoutput, electrical brain activity, oxygen consumption, tissue pH, tissuelactic acid level, or CO2 production. In some embodiments, the relativepreferred value is a target behavior of the trend of the value of themeasured characteristic and includes further adjusting the guidancebased on a difference between trend of the actual value of the measuredcharacteristic and the relative preferred value of the measuredcharacteristic. In some embodiments, the recurrent guidance guides theuser towards substantially obtaining and maintaining the relativepreferred value of the measured characteristic.

In some embodiments, the relative preferred value is a target value ofthe measured characteristic including further adjusting the guidancebased on a difference between the actual value of the measuredcharacteristic and the relative preferred value of the measuredcharacteristic. In some embodiments, the target value corresponds to thetarget timing relationship between the MSKC and the CC of the user. Insome embodiments, the recurrent guidance guides the user towardssubstantially obtaining and maintaining the relative preferred value ofthe measured characteristic.

Described herein are systems for favorably coordinating a timingrelationship between an MSKC of a rhythmic musculoskeletal activity of auser with a CC of the user. In general, the system may include a promptdevice, such that the prompt device is configured to provide recurrentlya movement guidance to the user for guiding performance of the rhythmicmusculoskeletal activity. In general, the system may include a sensor,such that the sensor is configured to provide a signal that correlatesto a cyclically-varying arterial blood volume in a tissue of the user.In general, the system may include a processor, coupled to the promptdevice and the sensor, such that the processor is configured todetermine an actual value of a measured characteristic of the signalthat varies with the timing relationship between the MSKC and the CC ofthe user, and further configured to adjust the movement guidance basedon the trend of the actual value so as to cause the actual value of themeasured characteristic to approach a relative preferred value of themeasured characteristic.

In some embodiments, the measured characteristic of the signal thatvaries with the timing relationship between the MSKC and the CC of theuser includes at least one of a pulse amplitude, a peak to valleymeasure of signal waveform curvature, a measure of signal waveform peakcurvature, a measure of signal waveform valley curvature, a measure ofsignal waveform complexity, and a measure of an asymmetry of the signalwaveform. In some embodiments, the relative preferred value of themeasured characteristic is a threshold crossing of an increasing trend,a threshold crossing of a decreasing trend, a local maximum, or a localminimum of the trend of the actual value of the measured characteristic.In some embodiments, the sensor technology includesphotoplethysmography, impedance plethysmography, laser-Doppler bloodflow, acoustic sensing, or arterial tonometry.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a system for determining a target MSKC to CC timingrelationship and guiding a user to the target MSKC to CC timingrelationship, in accordance with a preferred embodiment;

FIG. 2 illustrates a system for receiving cardiac, musculoskeletal, orphysiological cycle signals to determine a target MSKC to CC timingrelationship and to guide the user to the target MSKC to CC timingrelationship, in accordance with an alternative preferred embodiment;

FIGS. 3A-B illustrate flow charts for sensing, calculating, and guidinga CC and MSKC timing relationship(s) of a user, in accordance withcertain preferred embodiments;

FIGS. 4A-C illustrate a timing relationship between central arterialpressure waveforms, peripheral arterial pressure waveforms, anelectrocardiogram tracing, a targeted rhythmic musculoskeletalcontraction cycle, and a timing of sensed MSKC events of a user, inaccordance with preferred embodiments;

FIG. 5 illustrates a flow chart for guiding a user to a target MSKC toCC timing relationship using a CC sensor (e.g. an electrocardiogram) andan MSKC sensor (e.g. an accelerometer), in accordance with a preferredembodiment;

FIGS. 6A-G illustrates a series of photoplethysmography, ECG, andaccelerometer signals of a user, in accordance with preferredembodiments;

FIGS. 7A-B illustrate flow charts for synchronizing a timing of arhythmic MSKC with a timing of a CC of a user using a measure ofarterial blood pressure, volume, or flow (e.g. plethysmography), inaccordance with preferred embodiments;

FIG. 8 illustrates a treadmill system for sensing a CC and MSKC timingof a user and guiding a user to the target MSKC to CC timingrelationship, in accordance with a preferred embodiment;

FIG. 9 illustrates a biking system for sensing a CC and MSKC timing of auser and guiding a user to the target MSKC to CC timing relationship, inaccordance with an alternative preferred embodiment;

FIG. 10 illustrates a flow chart for calibrating a system fordetermining a target MSKC to CC timing relationship, in accordance witha preferred embodiment;

FIG. 11 illustrates a wrist-based device for calibration of a CC sensor,in accordance with a preferred embodiment; and

FIG. 12 illustrates a head-based device for calibration of a CC sensor,in accordance with an alternative preferred embodiment.

DETAILED DESCRIPTION

The following description of the preferred embodiments of the inventionis not intended to limit the invention to these preferred embodiments,but rather to enable any person skilled in the art to make and use thisinvention. Disclosed herein are systems and methods for favorablycoordinating musculoskeletal and cardiovascular or cerebrovascularhemodynamics.

In this disclosure, the terms cardiac cycle (“CC”), cardiovascularcycle, and cardiac pump cycle may be considered synonymous, referring tothe activity of the heart during a single, complete, heart pump cycle(equivalently, a single heartbeat). The terms heart rate (“HR”), cardiacor cardiovascular cycle rate, and cardiac pump cycle rate may beconsidered synonymous. Numerous key aspects of the cardiac pumpingcycle, as well as detectable signals that reflect those aspects, occuronly once per heartbeat. These include, for example, elements of theheart's electrical activity, corresponding periods of cardiac musclecontraction (systole) and relaxation (diastole), the filling andemptying of the chambers of the heart, the individual heart valvesopening and closing, and the associated arterial blood pressures andflows. Each of these aspects, elements, components, or events reoccurswith every heartbeat. Further, the phrases blood pressure, pressure, orarterial pressure may be used interchangeably, as when describingsensors, waveforms, or signals responsive to at least one of arterialblood pressure, volume, or flow, such as a plethysmographic sensor, forexample.

In this disclosure, the terms musculoskeletal activity cycle andmusculoskeletal activity pump cycle may be considered synonymous. Asdisclosed herein, MSKC equivalently may refer to the activity of the MSKduring a single, complete, MSK pump cycle (e.g. a single stride or steprunning, pedal push biking [½ revolution of the pedal], stroke swimming,or pull rowing). Numerous key aspects of the MSKC, as well as detectablesignals that reflect those aspects, occur only once per MSKC. One MSKCrefers to the activity of the MSK system that results in peripheralvascular blood pumping during a single cycle of the rhythmic physicalactivity of the user. Musculoskeletal activity rate (“MSKR”),musculoskeletal activity pump cycle rate, musculoskeletal pump rate, andcadence may be considered synonymous, not to be confused with the factthat the term cadence can alternatively be commonly used to reference amultiple of the true MSKR (e.g. bicycle RPM [“cadence” ] of 90→MSKR of180, because there are two MSK pumping activities, one per leg, for eachfull revolution of the bicycle pedals). Examples of common MSKRs duringphysical activity include stride frequency in walking or running, legpumping rate while pedaling on a bicycle, stroke rate when swimming orrowing, etc. Further, different MSKCs may occur simultaneously in asingle user at different rates. For example, a swimmer may kick withtheir legs at a multiple of the rate that they pull with their arms andeach of a rower's strokes includes both a pull and a push of the oars.In the following disclosure, the terms synchronize and coordinate, andderivatives of these terms, may be used synonymously to describe anytype of consistently repeated pump timing relationship.

Described herein are systems and methods for coordinating CC and MSKCpumping activities to achieve MCP. MCP is considered optimized for arhythmic physical activity when the CC and the MSKC are synchronized(i.e., coordinated) in a complimentary fashion such that the MSKC pumpsmaximal blood cumulatively into the central circulation (e.g. aorta)during early CC diastole, and the heart pumps blood maximally into thecentral circulation at the most overall favorable relative timing to theMSKC. As used herein, this optimal relative timing of the CC and MSKCpumps is generally considered the target MSKC to CC timing relationship.CC and MSKC pumping activities are coordinated to achieve MCP by guidinga user to a target MSKC to CC timing relationship, and MCP is achievedwhen a user attains the target MSKC to CC timing relationship. In someembodiments, a user is guided to achieve MCP. Alternatively, in certainother embodiments, a user is guided to avoid inverse MCP (iMCP) in whichthe two pumping systems are coordinated unfavorably. The systems andmethods described herein may take into account that, in some instances,a user may achieve MCP naturally during rhythmic MSK activity, at leastfor a period of time, without any external input.

Rhythmic MSK activity as described herein may refer to biking, running,rowing, walking, swimming, and/or any other type of rhythmic activity.Rhythmic may refer to any repeating pattern (e.g. 1, 2, 1, 2 . . . ; or1, 2, 1, 2, 3, 1, 2, 1, 2, 3 . . . ). For example, during running, therhythmic stepping pattern may comprise: left foot, right foot, leftfoot, right foot, etc., where the steps occur with every heartbeat orwith every other heartbeat. Alternatively, during rowing, rhythmic maycomprise each stroke of the paddle in the water, where the stroke istimed based on the heartbeat, but not each heartbeat or necessarilyusing the same number of heartbeats between each stroke. Additionally,different parts of the MSK system of a user may simultaneously maintaindifferent rhythms, e.g. during certain swimming strokes, a lowerextremity kick rate may occur at a higher frequency than an upperextremity stroke rate.

In some embodiments, the system monitors a MSKC to CC timingrelationship of the user and prompts, motivates, or otherwise guides theuser to reach a target MSKC to CC timing relationship and therebyachieve MCP. A user of the system described herein may be any personperforming rhythmic musculoskeletal activity. Peripheral or centralphysical locations adjacent to the circulation of a user, for example,locations on the arm, wrist or finger of an upper extremity, the earlobe or canal, forehead, temple, retina, or elsewhere on the head may bemonitored to determine a timing relationship from sensed hemodynamiceffects (e.g. changes in arterial blood flow, volume, or pressure). Asdescribed herein, the timing relationship may be the timing relationshipbetween the MSKC timing and the CC timing. In some embodiments, thetiming relationship may be described as a phase relationship of the CCand MSKC pumping activities or the signals responsive to the respectivepumping activities, or a time offset between them.

In further embodiments, a target HR may be chosen prior to or during anactivity, based, for example, on comfort, preferred MSKR, desiredeffort, type of run (e.g. intervals, speed, etc.), coached target,calibration run, or a calculation based on calculated and tested orentered maximum HR.

In some embodiments, a MSKC to CC timing relationship of a user may bemonitored and/or guided using an application on an electronic device,for example a mobile phone or a laptop. The application may runconstantly in the background, for example, in a head mounted“smartglass” heads-up display/processor, an ear mounted “smartheadphone” or earbud audio/processor, or in a wrist mounted “smartwatch”display/processor. The application may offer a prompt, such as an iconor audible signal that conveys that the HR is substantially an integermultiple of the MSKR, e.g. “HR≈step rate” during running or “HR≈2×steprate” during hiking up an incline. In some ambulation embodiments, theapplication may query the user whether or not the user would like tostep to the beat. In accordance with preferred embodiments describedherein, prompting a user to move to the beat may only occur when the HRand the MSKR of the user are naturally substantially aligned, forexample, when the user's HR equals approximately an integer multiple ofthe frequency of his or her MSK activity.

In some embodiments, information about a user may be tracked, usingappropriate sensors, before, during, and/or after one or more MSKactivities. This information may be used during calibration of a targetMSKC to CC timing relationship, for guiding the user to the target MSKCto CC timing relationship, and for tracking a user's progress toward thetarget MSKC to CC timing relationship during use of the system. Forexample, subjective information may be tracked, such as a difficulty,satiety, energy level, or satisfaction “index.” The index may rely onfeelings and/or emotions of the user regarding the exercise experienceand how the body feels at periods before, during, and/or after the MSKactivity. Other subjective information may be used, including pleasureand pain. Further, information including the amount of weight loss orgain that the user experiences may be tracked. For example, the systemmay enable a user to record his or her weight at a certain point before,during, and/or after the MSK activity. Weight data may be correlatedwith other measurements to provide useful information to the user.

In some embodiments, respiratory information is tracked. Suchinformation includes, for example, respiratory exchange ratio, minutevolume (VE), volume of CO₂ produced, volume of O₂ consumed, O₂ debt,and/or force of expiration. By tracking the user's respiratoryinformation, and by presenting trends or changes in the respiratoryinformation, the energy conservation advantage of the system is readilycommunicated to the user.

Other trackable information for calibrating, guiding, and measuringprogress during use of embodiments of the system may relate to skin,muscle, interstitial fluid, and blood characteristics. For example,monitoring continuous or intermittent glucose or insulin levels may beuseful, particularly for persons with diabetes. Alternatively oradditionally, lactic acid or pH levels may also be tracked. In someembodiments, retinal, facial, muscular, and/or cerebral blood flow maybe sensed and tracked. Retinal pulse embodiments may be captured, forexample, by cameras. Pupil reactions may also be monitored. Acute,chronic, central, and peripheral blood pressure may also be tracked.Stroke volume and cardiac output may be tracked. Examples of capturingbrain function and perfusion may extend beyond cerebral blood flow, toinclude EEG (electroencephalogram) sensed from a head mounted system ormeasures of cognitive function. HR variability may be measured to enabletracking of stress levels or other general health and fitnessinformation. Further, information may be tracked that relates to theintensity, duration, ergonomics, and effectiveness of an activity, suchas movement, acceleration, speed, magnitude of muscle contraction,and/or force per second. Sensed signals might include, for example,electromyography (EMG), accelerometry, pressure sensors, etc.

Other types of metrics may be measured, recorded, and/or used by thesystem during physical activity. In some embodiments, metrics mayinclude efficiency metrics. Exemplary physical activity relatedefficiency metrics may include watts/beat (e.g. power per heart beatwhile pedaling a bicycle); watts/HR; [Δdistance×Δelevation]/beat;Δdistance/Δelevation/HR; and [gradient×distance]/HR. Slope, tilt orinclination can be expressed in a variety of ways, including, but notlimited to 1) a ratio of the rise to the run, for example 1/20; 2) anangle, for example in degrees; and 3) a percentage called the “grade”(rise/run×100). Further exemplary metrics may include a “pulse-pace”,such as [heart beats]/mile; miles/beat; ft/beat, km/beat, watts/beat,strokes-mile, or rpm/mile may be monitored and tracked (wherein“beat”=heart beat).

Systems

FIGS. 1 and 2 illustrate a system for determining a target MSKC to CCtiming relationship and guiding a user to the target MSKC to CC timingrelationship, in accordance with a preferred embodiment. The system asshown in FIGS. 1 and 2 may be combined into one device or maintained astwo or more separate devices in communication with one another. Thesystem may be placed on or mounted to exercise or gaming equipment usedor worn by a user. A wearable system may include a chest strap, helmet,headband, hat, visor, sports bra, shoe, watch, wristband, armband, anklebracelet, headset, earpiece, earbuds, glasses/goggles, contact lens,embedded chip, patch, and/or any other type of adhesive, wearable, ormountable device. Equipment may include a bike, treadmill, ellipticaltrainer, stair stepper, rowing machine, boat, paddle, pacemaker, videogaming system, powered exoskeleton bionic devices, and/or any other typeof equipment used during rhythmic physical activity. Use andmanipulation of exercise equipment to determine a target MSKC to CCtiming relationship of a user and to guide a user towards the targetMSKC to CC timing relationship will be discussed in further detail belowin connection with FIGS. 8 and 9.

As shown in FIGS. 1 and 2, a system for determining a target MSKC to CCtiming relationship includes one or more sensors, detectors, or sensingelements 10 a, 10 b (collectively 10) for delivering or transmittinginformation to one or more processors/controllers 11. The processor 11,as shown in FIGS. 1 and 2, processes, converts, or otherwise transformsthe sensor information using hardware and software and transmits ordelivers the resulting relevant guidance and/or adjustment informationto at least one of a user input interface 12, user guidance interface13, or an equipment interface 14. Optionally, the system may include afront end 15, as shown in FIG. 2. The front end 15 pre-processes,transforms, separates, or otherwise deciphers information received fromthe one or more sensors 10 and transmits the information to theprocessor 11. In some embodiments, transmitting, delivering, orotherwise transferring information between system components may beaccomplished wirelessly (e.g. through cellular, Wi-Fi, Bluetooth,ultrasound, or ANT+ technologies), and/or through a hardwiredconnection. For example, the hardwired connection may include anelectrical connection, universal serial bus (USB), or FireWire, forexample Apple's IEEE 1394 High Speed Serial Bus.

In some embodiments, as shown in FIGS. 1 and 2, a sensor, detector, orsensing element 10 is used to detect a physiological parameter, feature,or metric and transmit the information about the physical parameter inthe form of a raw or pre-processed signal. A sensor technology 10 may,for example, include electrocardiography (ECG), accelerometry,electromyography (EMG), electroencephalography (EEG), plethysmography(e.g., photoplethysmography (PPG) or impedance plethysmography (IPG)),arterial tonometry, or use of a pressure sensor, a switch, a camera, agryroscope, a proximity sensor, a glucose sensor, a pH sensor, a lacticacid sensor, laser-Doppler blood flow, and/or an acoustic sensor (e.g.ultrasound, SONAR). In some embodiments, a physical parameter detectedby the sensor 10 may include repetitive features of a CC or a MSKC, asshown in FIGS. 4 and 6. In some embodiments, the features useful foridentifying the CC pump timing may correspond to an ECG R-wave, an ECGT-wave, an end of the ECG T-wave, a peak of a cardiovascular systolicpressure, a nadir of a diastolic cardiovascular pressure, and/or atransition point in a cardiovascular pressure of the user, as shown inFIG. 4. These features and their respective timings may be identifiedfrom the raw signals by processing algorithms programmed into processor11, or alternatively the feature identification process may beincorporated into the sensing device directly. Similarly, featuresuseful for identifying the MSKC pump timing may be determined usingalgorithms programmed into the processor 11 from raw signals sensed byone or more sensors 10 (e.g. 10 b), or alternatively incorporated intothe sensing device directly.

As described herein, a signal may include two or more characteristics.In some embodiments, a first characteristic of a signal may include arepetitive feature of a CC, for example a T-wave or an R-wave of theelectrical signal of the CC or a peak pressure of a plethysmographysignal, and a second characteristic of the signal may include arepetitive feature of a musculoskeletal activity, for example a steptiming of a user. In some embodiments, two or more characteristics maybe derived using processor 11 from one signal. For example at least oneof HR and MSKR and MSKR to CC relative timing information may be derivedfrom characteristics of a signal from the same plethysmogram or aplethysmographic sensor 10.

In some embodiments, as shown in FIGS. 1 and 2, a user input interface12 may receive information from the processor 11. The user inputinterface 12 may be configured to receive commands or cues from a userthat are delivered to the processor/controller 11, as well as configuredto deliver commands or cues from the processor/controller to a user ordevice/component. Commands may be tactile, audio, visual, or in anyother form. In some embodiments, tactile commands from the user mayinclude keypad strokes, actuation of switches or buttons, and/or touchinteractions delivered by the user. Additionally, vibrations, taps,electrical signals, or nudges are examples of commands that may beprovided to the user from the system. Audio commands may include thosereceived by the user input interface 12 from the user, the processor 11,the sensors 10, or the user guidance interface 13. Further, audiocommands delivered to the user may include commands that direct the MSKactivity of the user, including, for example, a metronome, the beat ofmusic, drum beats, changes in tonal qualities of an audible prompt,and/or games and words. In some embodiments, visual commands or cues mayinclude visual displays or prompts, analogue dials, graphs, movies,games, or any other type of viewable command. In certain embodiments,tactile guidance may include at least one of guidance on a timing,location, magnitude, and/or direction of MSK activity, using one or moreseparate means or skin locations for stimulating the user. For example,a mechanical or electrical tactile prompt may be provided to one or morelocations on the user's hand, wrist, head, or foot, depending on theplacement of the prompt device. In further embodiments, the magnitude,quality, or location of the prompt may be varied as to guide the user'sMSK activity, for example, to guide at least one of a user's speed,effort, or direction while walking or running.

As shown in FIG. 1, a system may include a user guidance interface 13.In some embodiments, the user guidance interface 13 may be combined ormerged with the user input interface 12, such that the user inputinterface 12 is the user guidance interface 13. Alternatively, the userguidance interface 13 may be combined or merged with an equipmentinterface 14, as shown in FIG. 2, such that the equipment interface 14is the user guidance interface 13. As described herein, guidanceincludes enabling a user to obtain and maintain a target MSKC to CCtiming relationship.

In some embodiments, the user guidance interface 13 may include a promptdevice that provides a recurrent prompt (guidance) at a prompt rate tothe user as a timing indication for performance of the rhythmicmusculoskeletal activity. The prompt device may be controlled by theprocessor 11. In some embodiments, the prompt rate may be substantiallyequal to a HR or a cadence of a user. In other embodiments, a HR of theuser may be substantially an integer multiple of the prompt rate. Insome embodiments, predetermined target cadences or prompt rates may beavailable to a user. For example, the target cadences (i.e. to achievethe target MSKC to CC timing relationship) may be based on a user'snatural or preferred cadences, type of activity (e.g. walking vs.jogging vs. running a competitive 5 K), duration of activity, gender,age, fitness level, other demographic information, user anatomy (e.g.height, weight), or other diagnostic information.

Timing of guidance signals may initiate automatically, by user requestthrough a user input interface 12 when HR and MSKC timing are nearlyaligned, or the user may be signaled or reminded when the guidance isavailable or appropriate through user input interface 12. The guidancemay be recurrent. In some embodiments, the guidance may fade away orbecome imperceptible as long as the user achieves and maintains thetarget MSKC to CC timing relationship. The guidance may resurface orbecome perceptible if the user fails to sustain the target MSKC to CCtiming relationship during a given time period. In some embodiments, thesystem senses that a user responds late or early to guidance and adjuststhe guidance automatically to guide the user to the target MSKC to CCtiming relationship. Alternatively, in some embodiments, a user mayadjust the guidance manually, for example to increase or decrease atarget MSKR or HR, such that the target MSKC to CC timing relationshipdictated by the system is reset accordingly.

In some embodiments, the user guidance interface 13 of the system mayinclude music to guide the MSKC timing of the user. Accordingly, a usermay be prompted with music having a beat that will guide the user to atarget MSKC to CC timing relationship. Music may be selected inreal-time, pre-selected, or automatically selected, for example, inresponse to the measured or known beat frequency of the songs and theactual or target MSKR of the user. Playlists or sequences of musicalrenditions may be defined by the user, or suggested by the system to theuser. Playlists may vary depending on the HR, MSK activity, and otherstates desired for a given physical activity. Musical selections used toprompt MSK activity timing may change in beat frequency, beat volumerelative to overall music volume (e.g. drum beat, base guitar,concurrent metronome), overall music volume, or other features to guidethe user. In an exemplary embodiment wherein a drum beat of a musicaltrack is the timing prompt for a user, the volume of the drum beatprompt relative to the volume of the musical track may graduallyincrease above a baseline or added on top of a the track, as theaccuracy or consistency of the user's timing relative to the promptdecreases. Alternatively, the volume of the drum beat prompt relative tothe remainder of the musical track may decrease or return to a baselinein response to a sustained improvement in the user's MSKC timingaccuracy or consistency. In certain embodiments, the system may furtherbe configured to constantly adjust the playback speed of the music tofine-tune the beat rate used to guide the user. Additionally, the musicwith altered playback speed can be pitch-corrected to maintain theproper intonation.

In some embodiments, the system may deliver a new prompt or modify anexisting prompt in order to indicate to the user the need to moreaccurately or consistently step to the underlying beat of the deliveredmusic and/or the need to make corrections in MSK activity such aschanges to stride length, degree of knee bend, heel strike, toe-off,exercise resistance, bicycle gear, or arm swing. In some embodiments, auser may hear a change in prominence of the underlying beat of a song(for example the base drum, base guitar, and/or an added metronome beat)relative to the rest of the song as an indication to the user that he orshe needs to more accurately move with the timing of the underlying beatof the music, improve identification of the prompt within the music, orpay better attention to moving to the beat. Musical communication may bepre-defined by the user so as to suit his or her understanding orpreferences. A tactile prompt can be provided at a prompt rate inaddition to or instead of an audible prompt.

In some embodiments, guidance may be provided by game embodiments thatutilize metrics. For example, one embodiment of the system includessensors that continuously run in the background during any rhythmicphysical activity. In this embodiment, information from sensors and/orMSK activity guidance may be offered, made available, or automaticallyturned on as a biofeedback prompt when, during the course of thatactivity, the HR naturally approaches or approximates an integermultiple of the MSKR of the user (e.g. 1×, 2×, 3× . . . ). For example,biofeedback may be provided audibly via an earbud or other earpiece;visually via head-mounted smart eyeglasses or contact lenses or asmart-watch; via tactile feedback from a smart-watch, smart-headset, orsmart-shoe; or via any other type of biofeedback enabled device, asdescribed herein.

Games and gaming systems may be leveraged, including, for example, anXbox Kinect type audio-visual gaming hardware that includes cameras thatcan visualize at least one of the MSKC and the CC of the user, as wellas provide at least one of audio, visual, and tactile MSKC timingguidance to the user. In embodiments of the system and method, MSKCtiming inputs may be received and/or captured by a camera(s), such thatthe camera(s) may capture other MSK activities beyond foot strike timingand/or arm motion timing. Further, CC timing inputs may be acquired bygaming sensors. For example, a camera may be used to monitor CC timingvia at least one of subtle rhythmic skin color changes, smalltemperature (IR) changes, and tiny rhythmic movements (e.g. headbobbing) caused by arterial blood flow and pulsatile pressure changesduring the CC. Gaming system embodiments may include wearable sensorsfor ambulatory versions, whereas a video camera(s) may enable sensing ofMSKC timing without wearable sensors. Alternatively, an accelerometer,other position/orientation sensors, floor based pressure sensors, or EMGmay be used to measure the whole body or specific limbs or muscles, suchas number of muscles, force of contractions, magnitude and/or speedand/or acceleration of movement that achieves the target MSKC to CCtiming relationship. A game may be configured to give points or otherscalable credit for increases in well-timed physical activity metricsrelative to timing targets, including foot strike, limb movementmetrics, and other body movement metrics. Limb movement metrics mayinclude speed, acceleration, change in center of mass, or body movement.Body movement metrics may include speed, acceleration, center of mass,side-to-side movement, or change in height.

Algorithms used by the system for determining a user's actual CC timingmay include calibration or corrections for arterial pulse transit timerelated to at least one of the user's height, age, HR, pulse amplitude,or a CC measurement location, for example. Acquisition of CC timing mayinclude analysis and/or amplification of plethysmographic signals, skincolor changes, and/or head movements (e.g. following set points on faceof the user) related to the pulsatile flow of arterial blood.Alternatively or additionally, acquisition of CC timing may includeinformation from other sensors and wearable devices, for example, anECG. As illustrated in FIGS. 11 and 12, an ECG signal may be obtainedsimultaneously with an arterial pulse signal, enabling calibration ofthe pulse transit delays in monitoring the CC timing, because theheart's electrical activity (ECG) reliably reflects the true timing ofthe CC due to the speed with which electrical signals travel through thebody, while pulse pressure signals travel much more slowly at variablespeeds that are effected by user size, age, arterial anatomy, sensorplacement, and cardiovascular physiology (e.g. cardiac contractionforce, blood pressure, hyrdration, blood viscocity, temperature,vasoconstriction, arterial wall stiffness, etc.)

Methods of Using Sensor Technologies for Favorably Coordinating CC andMSKC Timing

FIGS. 3A-B illustrate flow diagrams of a system in accordance withpreferred embodiments that include sensing a CC and MSKC timing of auser. As shown in FIGS. 3A-B, the system senses CC timing 16 and MSKCtiming 17 of a user. Any number of sensing technologies may be used, forexample ECG or plethysmography can be used to sense CC timing.Optionally, as shown in FIG. 3A, additional (e.g. 2^(nd), 3^(rd),4^(th), N^(th)) MKSC timings 18 of a user may be sensed by the system,each being compared in step 21 to the CC timing of the user and/or toeach other.

FIG. 3A illustrates a flow diagram for sensing a CC and MSKC timing of auser, for example using ECG and an accelerometer. As shown in FIG. 3A, aprocessor is used to identify a valid CC 19 and a valid MSKC 20 eventtiming. A valid CC event 19 may be any point or portion of a CC or otherinformation that conveys CC timing information, as discussed above. Avalid MSKC event 20 may be any point or portion of a rhythmic physicalactivity that conveys MSKC timing information, as discussed above. Validevents 19 and 20 may correspond to those that pass signal processingmetrics designed to reject false events caused by noise or otherinterferences that are unrelated to the user's heartbeat or relevant MSKactivity. For example, detected events in the CC signal that occur toosoon after a previous valid CC event and that would otherwise representa non-physiologic HR or one that is far greater than the user's recentvalid HR may be rejected.

In some embodiments, an actual (e.g. real-time) relative MSKC to CCtiming is determined and compared to a target relative MSKC to CC timing21. The difference between the actual relative MSKC to CC timing and thetarget MSKC to CC timing 21 is calculated, representing a differencevalue in a feedback loop, which is used to determine a correction, ifneeded, in any guidance a user requires to achieve the target MSKC to CCtiming relationship. In some embodiments, the timing relationshipbetween the first MSKC timing and the second MSKC timing may be obtainedusing a first processor. Further, in some embodiments, the timingrelationship between the second sensed MSKC timing and the CC timing maybe obtained by the same first processor or on a second processor. EachMSKC to CC and MSKC to MSKC timing relationship is characterized by theelapsed time between the occurrence of one component of the first signaland the occurrence of one component of the second signal. In someembodiments, this timing relationship may further be normalized (i.e.,divided) by the elapsed time between two subsequent occurrences of theone component in the first or second signal. Additionally, in someembodiments, the timing relationships may be recalculated on acontinuous real-time basis, at random times, or at various intervals.

In some embodiments, correction values 9 may be computed to adjust thetiming of the guidance as a function of the correction values. Thecorrection values may be based on the CC timing of the user, the firstor second MSKC timings of the user, a relative MSKC to CC timing, thedifference to a target MSKC to CC timing relationship, or one or moretime delays, offsets, or other information. Further, a user may beguided or prompted to achieve the target MSKC to CC timing relationshipbased on the adjusted timing of the guidance 23. In some embodiments,the flow diagrams of FIGS. 3A and 3B may repeat in a loop function.Alternatively, the user may achieve and maintain the target MSKC to CCtiming relationship, and thus not require any adjustment in theguidance. In some embodiments, the loop function may be used tocalibrate a system to one or more physiological preferences of a user,as will be described below. For example, the system may adjust theguidance to a user that steps early or late relative to a target MSKC toCC timing relationship upon receiving the guidance. Alternatively, auser may naturally achieve MCP occasionally during certain rhythmicmusculoskeletal activities. Thus, the system may be calibrated to adjustthe guidance to enable the user to maintain the natural MCP of the user.

FIG. 3B illustrates a flow diagram for sensing a CC and MSKC timing of auser, for example with PPG or IPG, in accordance with a preferredembodiment. As shown in FIG. 3B, the system may sense a signal from asensor 16 that correlates to the CC of a user to calculate a HR 6, andanother signal of the user using a sensor 17 that correlates with theMSKC 17 in order to calculate an MSKC rate (MSKR), using any number ofsensing technologies. In some embodiments, signals that correlate toboth the CC and MSKC of a user may be obtained from a single sensor, 16or 17. For example, as will be described more fully below, aplethysmographic sensor can be used to sense one or more of CC timing,MSKC timing, and information regarding MSKC to CC timing relationships.In some embodiments, the timing relationships may be recalculated on acontinuous real-time basis, at random times, or at various intervals.

In some embodiments, as shown in FIG. 3B, if the HR of the userapproaches an integer multiple of the MSKR ((n×MSKR)−HR, where n=anyinteger 1-10) of the user (with an absolute difference <x per minute) 5,then a characteristic (or set of characteristics) of the sensor signalcan be used to guide the user towards a target MSKC to CC timingrelationship. For example, the sensor signal may be a PPG and thecharacteristic may be pulse amplitude in the PPG or, in anotherembodiment, a combined measure of pulse amplitude and pulse complexity.The change in the value of the characteristic that represents the MSKCto CC timing relationship may be calculated to determine an amount andnature of guidance a user requires to achieve the target MSKC to CCtiming relationship 8, as will be described in further detail inassociation with FIGS. 6-7. In some embodiments, correction values 9 maybe computed to adjust the timing of the guidance as a function of thecorrection values. A user may be guided or prompted to achieve thetarget MSKC to CC timing relationship based on the adjusted timing ofthe guidance 23. In other embodiments, as described later in FIG. 7, theMSKC timing may be held constant and the user may be guided to thetarget MSKC to CC timing relationship by guiding changes in CC timing byguiding changes in the effort invested in the MSK activity, e.g. changesin MSKC speed, acceleration, power, resistance, stride length, orincline during exercise. In some embodiments, the flow diagram of FIG.3B may repeat in a loop function 4, as described above. Alternatively,the user may achieve and maintain the target MSKC to CC timingrelationship, and thus not require any adjustment in guidance. In someembodiments, the loop function may be used to calibrate a system to oneor more physiological preferences of a user, as will be described below.

In accordance with the description above, FIGS. 4A-C illustrate a timingrelationship between central arterial pressure waveforms, peripheralarterial pressure waveforms, an electrocardiogram tracing, a targetedmusculoskeletal contraction cycle, and a timing of sensed MSKC events ofa user, in accordance with preferred embodiments. FIGS. 4A-C are shownaligned horizontally in time to each other for the purpose ofillustration, such that the information has been sensed, detected, orcollected by one or more sensors or sensor technologies as describedabove and processed by a processor. The sensed timing relationships, asshown in FIGS. 4B and 4C, may be used to determine the MSKC to CC timingrelationship of a user. In general, central arterial waveform 32represents exemplary arterial pressure in the aorta of an individual atrest, while waveform 34 represents at least one of an exemplarysimultaneous peripheral arterial pressure, flow, and/or volume (e.g.peripheral PPG or blood pressure signal) of the same individual. Asshown in FIG. 4A, simultaneously monitored exemplary central arterialpressure waves 32 and peripheral arterial pressure waves 34 aretemporally offset from one another due to arterial pulse transit time,the time required for the arterial pressure waves to propagate throughthe arterial circulation from the heart and central circulation to agiven peripheral location in the body of the user. Each of thesewaveforms exhibit changes in arterial pressure caused by the systolic 25and diastolic 29 portions of the CC, which may include a peak systolicpressure 31, that repeats at the HR of the user.

Further, as shown in a simultaneous electrocardiogram (ECG) tracing inFIG. 4B, the representative ECG signal 22 (illustrative of the tracingone might obtain, for example, from a chest strap lead), includesvarious different waves including P-waves, Q-waves, R-waves, S-waves,and T-waves. R-waves 24 (24 a, 24 b, and 24 c) represent depolarizationof the ventricular muscle of the heart. R-waves 24 repeat with eachheartbeat at a HR of a user and are readily identifiable in an ECGsignal 22. Therefore, in some embodiments, R-waves 24 may be utilized inthe measurement of the HR via the measurement of the duration of R-to-Rintervals (RRI) 26. The T-wave 28 reflects ventricular repolarization.End T-wave 30 may be used as a marker of the approximate timing ofaortic valve closure, which marks the beginning of diastole during thepumping cycle of the heart. The timing and characteristics of thesewaves in FIGS. 4A-B, like other similarly sensed waves and wave markers,are representative of the timing of the CC and therefore may be used incalibrating, guiding, and/or tracking a user and to coordinate MSKC andCC hemodynamics to achieve a target MSKC to CC timing relationship.

As shown in FIG. 4C, skeletal muscle contraction cycles 36 includeperiods of relaxation and contraction, as indicated by the dotted linesin FIG. 4C and, with respect to the timing of a user's CC shown in FIGS.4A and 4B above, may include a target MSKC to CC timing relationship, inaccordance with embodiments of the methods and systems. While exemplaryskeletal muscle contraction/relaxation cycles 36 and prompts 35 areillustrated in FIG. 4C, arterial and venous MSK induced blood pumpingalso may be caused by changes in inertia during many types of rhythmicphysical activity. Also, while exemplary central 39 and peripheral 40arterial waveforms are illustrated in FIG. 4C, other important factorsin optimizing MSKC blood pumping and target MSKC to CC timingrelationships during many types of physical activity may take place butare not illustrated by the arterial waveform, for example venous bloodpumping from MSKC induced skeletal muscle pumping.

As is illustrated in FIG. 4C, both the CC and MSKC pressure waves can besensed simultaneously by a sensor responsive to changes in the arterialblood pressure, volume, or flow. Further, as is illustrated in FIG. 4C,when HR and MSKR are equal, then the MSKC may create pressure waveswithin the arterial circulation that are substantially at the samefrequency as the pressure waves created by the CC. Exemplary arterialpressure waveform 39 represents an approximation of the central arterialpressure during MCP, wherein maximal MSK induced blood pumping is seenin the central arterial circulation during early diastole. This samewaveform 39, however, may also represent an approximation of theperipheral arterial pressure, for example at the head of a user, duringMSK-induced iMCP due to inertial effects and/or the impact of pulsetransit time on arterial waveform shape and timing. Waveform 39, whenobserved centrally during MCP, may be very similar in appearance to thecentral waveform that can be produced during other types of medicallyinduced therapeutic counterpulsation techniques, including intra-aorticballoon counterpulsation (IABP) and external counterpulsation (ECP).Waveform 39 may also illustrate the shape of a target peripheralarterial waveform during ECP and IABP counterpulsation, because, withthe user at rest, the pressure flow waves created by the two favorablycoordinated pumps (e.g. CC & ECP pumps) can maintain their relationshipto one another as the waves propagate through the circulation of theuser. Further, an exemplary peripheral arterial pressure waveform 40, asmight be sensed from a location on the head of a user during MCP isillustrated, which also represents an approximation of an exemplarycentral arterial waveform during iMCP.

Because physical activity can cause blood pumping via both MSKcontraction/relaxation cycles and through changes in inertia, thelocation of an arterial sensor can be important in determining thewaveform timing characteristics of the waves created by each of theseseparate pumping mechanisms. For example, (1) pulse transit time from aCC is increased with the arterial distance of the sensor from the heart;(2) pulse transit time from a skeletal muscle contraction pumpinglocation is also increased with the arterial distance from the skeletalmuscle doing the pumping; while (3) the inertial pump waveforms occurconcurrently with the changes in inertia that create them, but theiramplitude and direction can be dramatically effected in theirrelationship to skeletal muscle pump and the CC pump waveforms by thelocation of the sensor, for example, at, above, or below the heartand/or skeletal muscle pump (e.g. sensor at head vs. chest vs. foot ofthe user during running) or in other examples, on a limb heldsubstantially parallel to the ground vs. one held substantiallyperpendicular to the ground in one direction vs. one held substantiallyperpendicular to the ground in the opposite direction (e.g. wrist basedsensor with hands held above the head vs. hands kept at lower chest vs.hands kept below the waist during running). Because wave amplitude andtiming in response to a CC and MSKC can change with different activitiesand physiologies and sensor locations, calibration of the system touser, physiological variables, sensor location, and specific physicalactivity can be important.

As shown in FIG. 4C, examples of target MSKC to CC timing relationshipsare illustrated, comprising periods of skeletal muscle contractionduring central diastole 29, as shown in FIG. 4A, followed by periods ofrelaxation during central systole 25. In exemplary target MSKC to CCtiming relationship 36, the user has been guided to perform the portionof the rhythmic MSK activity that results in maximal MSKC blood pumpingto begin at timing prompts 35 (black triangles) that repeat with eachinstance of the CC such that the ratio of MSKC:CC occurrences is 1:1.Alternatively, the MSKC prompts may be timed at the same location in theCC, but less frequently (e.g. with every other CC (1:2), every third CC(1:3), or every fourth CC (1:4)), wherein the HR is an integer multipleof the MSKR. As shown in FIG. 4B, % R-R interval scale 38 provides agraphical representation of the percent of the R-to-R interval (RRI) 26nomenclature, one RRI representing one full CC. % RRI may be computed asthe amount of time between an MSKC event and the most recent prior CCevent, divided by the amount of time between successive CC events,multiplied by 100. For example, 0% and 100% of the RRI represent thetiming of the R-waves (e.g. 24 a, 24 b, 24 c, etc.) in the CC, while 25%of the RRI is a quarter of the way between successive R-waves, and 50%is the mid-point between two sequential R-waves 24 of a CC. Scale 38 ofthe RRI may alternatively be expressed fractionally as a value from zeroto one, in units of degrees between zero and 360 degrees, or in radiansbetween zero and 2π radians (e.g., 25%=0.25=90 degrees=1.57 radians),equivalent to the percentage terminology. Values greater than 100%describe events in a subsequent RRI (e.g., 130% represents a 30%location in the following interval). Thus, the RRI may be used to alignprompts and musculoskeletal contractions within the same location ofeach CC over time.

In some embodiments, multiple MSK activities, involving different musclegroups across the user's body, may be performed simultaneously orsequentially by a user, with each of these activities having its ownMSKC timing and either a shared or unique target MSKC to CC timingrelationship. In such a scenario, the relative timing of each MSKC to CCmay confer separate cumulative hemodynamic effects on the central andperipheral circulation of a user, thereby impacting the magnitude ofoverall MCP or iMCP. MCP is considered optimized for a rhythmic physicalactivity when the CC and the MSKC are favorably coordinated so as togenerate early diastolic pressure waves in the central circulationsimilar to those of waveform 39 in FIG. 4C. In some embodiments, it maybe preferred to vary the target MSKC to CC timing relationship tooptimize hemodynamics for different simultaneous or sequential MSKactivities. Further, guiding a user to accomplish MCP or other MSKC toCC timing relationships may be desired, for example, in order to alterblood flow to specific MSK or non-MSK tissues, for example to improvecerebral perfusion.

FIG. 5 illustrates a flow chart for guiding a user to a target MSKC toCC timing relationship. A method for guiding a user to a target MSKC toCC timing relationship of a preferred embodiment includes detecting afirst signal responsive to a CC timing of a user using a first sensorS500; determining a HR of the user using a at least a portion of thefirst signal detected by the sensor S510; providing a recurrent promptfrom a prompt device to the user as a timing indication for performanceof a rhythmic MSK activity S520; detecting a second signal responsive toa rhythmic MSK timing of the user that repeats at a musculoskeletalactivity cycle rate (MSKR) of the user using a second sensor S30;determining an actual MSKC to CC timing relationship between MSKC and CCsignals S540; comparing the actual timing relationship of the CC andMSKC signals to a target timing relationship of the CC and MSKC signalsS550; and adjusting the timing indication of the recurrent prompt fromthe prompt device to the user based on the difference between the actualtiming relationship and the target timing relationship so as to reducethe magnitude of the difference S560. The method repeats by looping backfrom step S560 to S500, with the net effect of recurrently prompting andguiding the user so as to reduce the magnitude of the difference. Insome embodiments, the method preferably uses an accelerometer and an ECGto determine actual and, in some embodiments, target MSKC to CC timingrelationships of a user, although any CC and MSKC sensor or sensorcombination may be used as described above in connection with FIGS. 1and 2.

As shown in FIG. 5, step S500 includes detecting a first signalresponsive to a CC timing of a user using a first sensor. Further, stepS510 includes determining a HR of the user using at least a portion ofthe first signal detected by the first sensor. In some embodiments, a CCsignal, or a portion of the cardiac signal, may include any recurrentaspect or feature of a CC, as described above, for example an R-wave ofan ECG, a systolic peak of a plethysmogram, or a Fourier transform ofeither of these exemplary signals.

As shown in FIG. 5, step S520 includes providing a recurrent prompt froma prompt device to the user as a timing indication for performance of arhythmic MSK activity. In some embodiments, the recurrent prompt repeatsat a prompt rate such that the HR is substantially an integer multipleof the prompt rate.

As shown in FIG. 5, step S530 includes detecting a signal responsive toa rhythmic MSK timing of the user that repeats at a MSKR of the userusing a second sensor. Step S530 functions to determine a MSKC timing ofa user, such that an actual MSKC to CC timing relationship may becalculated as shown in step S540. In some embodiments, one or moresensors, for example an accelerometer, EMG, or any position/orientationsensor, may be used to sense aspects of an MSKC of a user, such that anactual MSKC to CC timing relationship may be calculated. For example,maximal MSK muscle contraction may be synchronized with the beginning ofdiastole in the CC of the user, as shown in FIGS. 4A-C. In someembodiments, step S530 may further include determining the MSKR of theuser using the data from the second sensor with a processor. In someembodiments, the sensor used to sense the CC of a user (S500) may be thesame sensor used to sense the MSKC (S530) of the user. Alternatively,two or more different sensors may be used to determine a CC and MSKC ofthe user.

As shown in FIG. 5, step S540 includes determining the actual MSKC to CCtiming relationship between first and second signals. The actual timingrelationship may be the measured timing relationship between the MSKCtiming and the CC timing. For example, the actual MSKC to CC timingrelationship of a user may correspond to MCP, to iMCP, or somewhere inbetween. Generally, most users not prompted to do otherwise willunintentionally vary in their MSKC to CC timing relationships during arhythmic MSK activity.

As shown in FIG. 5, step S550 includes comparing an actual timingrelationship of the CC and MSKC signals determined in step S540 to atarget timing relationship of the CC and MSKC. Step S550 preferablyutilizes a target MSKC to CC timing relationship that enables a user toachieve MCP. In some embodiments, the target MSKC to CC timingrelationship of a user may correspond to a condition when the CC and theMSKC blood pumps work in a complimentary fashion. In certain otherembodiments, a target MSKC to CC timing relationship for a user maycorrespond to, for example, simply avoiding persistent alignment ofmaximal MSKC blood pumping of the user with a peak of a systolicarterial pressure signal of the user so as to prevent the two pumpingsystems from persistently working against each other.

As shown in FIG. 5, step S560 includes adjusting a timing indication ofa recurrent prompt from the prompt device to the user based on adifference between the actual timing relationship and the target timingrelationship so as to reduce the magnitude of the difference. Step S560preferably functions to guide the user towards the target MSKC to CCtiming relationship. As shown in FIG. 5, step S560 loops back to stepS500 so as to repetitively update the recurrent prompt and guide theuser towards substantially obtaining and maintaining the target MSKC toCC timing relationship. In some embodiments, if the actual MSKC to CCtiming relationship of the user determined in S540 is associated withMCP (the target relationship of S550), the system functions to provide arecurrent prompt to the user that maintains the user at that timingrelationship. In some embodiments, the recurrent prompt provided in S520may comprise an audible or tactile metronome beat or a musical beat,wherein the beat frequency corresponds to the prompt rate. Furthermore,the prompt rate may continue persistently at the same frequency when instep S560 no adjustments to the prompt timing are indicated or for up toa pre-defined period of time when signals from S500 and/or S530 and thecomputations of S540 become temporarily disrupted.

FIGS. 6A-G illustrate a series of PPG signals of a user 41, 42, 43, 46,47 and 610, in accordance with a preferred embodiment. As describedabove, sensors utilizing plethysmography (e.g. PPG or IPG) may be usedwithin a system to favorably coordinate a timing of a rhythmic MSKC of auser that repeats at a MSKR of the user with a timing of a CC of theuser that repeats at a HR of the user. In general, plethysmographysignals from a blood-perfused tissue include a pulsatile component(“AC”) and a non-pulsatile component (“DC”), reflecting the short-termtime varying changes in local blood volume and overall raw signallevels, respectively. As is the case in FIGS. 6A-G, plethysmographysignals are typically presented graphically after normalizing (dividing)the signal by the recent average DC values to remove the influence offactors unrelated to the blood volume changes. The signal's “pulseamplitude” (PA=100×AC/DC as a percentage, sometimes also referred to aspercent modulation amplitude or perfusion index) is an indicator ofpulsatile signal strength and correlates to the relative changes inblood volume in the underlying tissue. For example, the pulse amplitudesof the PPG signals plotted in FIGS. 6A-F vary between approximately 2%and 6%, corresponding to the peak-to-valley heights of the envelope.

In some embodiments, plethysmography may be used collectively todetermine at least one of a CC rate, a CC timing, an MSKR, an MSKCtiming, a MSKC to CC arterial blood flow or pressure interaction, a MSKCto CC timing relationship, a target MSKC to CC timing waveform, and atarget MSKC to CC timing relationship, and may function to guide a userto a target MSKC to CC timing relationship. For example, a sensor ofblood volume, pressure, or flow, such as a PPG sensor, may be used aloneor in combination with one or more additional CC or MSKC sensors toprovide reliable identification, achievement, and maintenance of atarget MSKC to CC timing relationship. For example, to derive a HR of auser using a PPG sensor alone, instances of at least one feature of thePPG signal that repeats at the HR of the user (e.g. peak regularlyoccurring signal amplitude, P, illustrated by peaks 31 in FIGS. 4A, 4C,and 6D) may be identified by a processor, with HR calculated from therecurring time interval between each instance (the heart's beat-to-beator P-to-P interval), wherein HR=heartbeats/minute=[1minute÷(beat-to-beat interval in minutes)].

In some embodiments, the same PPG signal may also be used to derive theMSKR during rhythmic physical activity by identifying instances of oneor more features of the MSKC and CC wave interaction patterns in the PPGsignal. For example, when two waves in the same system occur atdifferent but similar frequencies, a characteristic beat pattern (FIG.6A) may be created in which the waves repeatedly go back and forthbetween overlapping 46 (resonance) and separating 47, with a maximalbeat wave amplitude happening when the two waves occur at the same timein the same location 46. In the event that the MSKC induced arterialpressure waves are from a single predominant rhythmic MSK pump, theresulting recurring increase and decrease in beat wave amplitude occursat a beat frequency that is the difference in the frequency between thetwo separate recurring CC and MSKC induced waves. Therefore, once the HRhas been calculated from data obtained via the PPG signal (as described,or via one or more other CC sensor systems), the MSKC frequency may becalculated by adding or subtracting the beat frequency of the PPG, whichmay be possible if the HR and MSKR are close enough to one another thatthe beat pattern of the overlapping MSKC and CC waves is identifiable.There are multiple simple ways to determine whether the beat frequencyshould be added or subtracted from the HR, for example, the wavemorphology as seen in an asymmetrical shape of the beat pattern of thePPG, as shown in FIG. 6A, may be reversed when the MSKR is higher thanthe HR. Alternatively, an additional sensor, such as an accelerometer,may be used to identify a separate MSKR signal, which will be describedin further detail below. In some embodiments, the relative timing,shape, and magnitude of the signals from pressure, volume, or flowsensors at different anatomical locations vary due to pulse transittimes (on the order of tens to hundreds of milliseconds), with amagnitude that generally increases as a function of the sensor'sdistance from the blood pump that has generated the sensed change insignal. Conversely, electrical sensors (e.g. ECG, EMG, EEG) senseelectrical signals that travel from their sources at nearly the speed oflight. Thus, delays due to anatomical location are imperceptible andclinically irrelevant. The increase in the magnitude of the delay (pulsetransit time) with the distance from the heart to the peripherallocation at which the waveform is measured, means that, for example, anincrease in the size of the individual (e.g. height or length of limbfor a limb-based plethysmographic sensor) might be a factor in generallyincreasing pulse transit time in that individual over individuals ofsmaller size, all else being equal. Other factors may also influencearterial pulse transit time delays and wave morphologies, includingvascular attributes (e.g. arterial stiffness, size), the type of MSKactivity, blood effects (e.g. volume, viscosity), and cardiac effects(e.g., contractility). These pulse transit time delays and other offsetsmay be accounted for in determining a target MSKC to CC timingrelationship and/or in computing an actual MSKC to CC timingrelationship.

FIG. 6A illustrates an exemplary PPG signal 41 observed at the foreheadof a user running at a step rate slightly slower than the HR of theuser. The slightly slower step rate of the user results in the userstepping, on average, slightly later in the CC with each step, asindicated by the points in 44 which indicate the MSKC to CC timing as a% RRI (0-100%) of each step of the user. As shown in FIG. 6A, thedifferent contributing wave frequencies combine in the PPG to yield theobserved beat phenomenon, wherein the peak arterial blood volume wavesregularly oscillate in magnitude between maximal 46 and minimal 47 sizeat a rate per minute equal to the difference between the HR and the steprate. In some embodiments, beat phenomenon 46-47 is a result of theregular, simultaneous occurrence of separate arterial pressure wavepeaks from MSK activity vascular pumping and the CC pumping. Theseseparate pressure waves, created at different frequencies, cycle betweenbeing substantially separate 47 to being progressively more on top ofone another and therefore substantially combined 46 then back again,repetitively, leading to regular oscillations in the magnitude of theperiodic arterial blood volume, as shown in FIGS. 6A, D, F. Further, thefrequency of the beat phenomenon may also be used as an input into aprogram or delivered to a processor that calculates the step rate oncethe HR is known, or calculates the HR once the step rate is known (e.g.from a separate accelerometer signal).

Further, additional characteristics of the PPG wave may reflect theactual timing of the MSKC relative to the timing of the CC. In someembodiments, signals may be processed to identify target PPG waveformcharacteristics and patterns that correspond to desired MSKC to CCtiming relationships. For example, values that represent PPG morphology,overall DC signal amplitude, pulse amplitude, average amplitude, changesin amplitude, rates of changes in amplitude, and averages andprogressions thereof, may be provided to a processor where they may beused to calculate a correction value for adjusting guidance to a userthat, when generally followed by the user, functions to reduce thedifference between the actual MSKC to CC timing relationship and thepreferred MSKC to CC timing relationship. In one embodiment, a processormay initially calculate appropriate guidance of timing to guide the userto achieve an MSKC rate (e.g. step rate) that is substantially equal toHR. In another embodiment, such initial guidance is not provided, andthe system initiates guidance once the PPG signal begins to exhibitgeneral behaviors chosen as indicators that a preferred MSKC to CCtiming would be readily achievable with user guidance.

In some embodiments, as shown in FIG. 6A, a periodic change in pulseamplitude of the PPG waveform may be present, indicating that the useris stepping at a timing relative to the CC timing that slowly changesover time during the rhythmic musculoskeletal activity. The processormay identify one or more characteristics of the PPG waveform thatcorrelate with relative MSKC to CC timing (e.g. pulse amplitude), whilesimultaneously identifying a marker of optimal relative MSKC to CCtiming, for example a reduced or minimum HR (HR_(min)) when compared toHR during an alternative MSKC to CC timing. As shown in the exemplaryPPG signals in FIG. 6C when the PPG amplitude is compared to recent PPGamplitudes 46 of FIG. 6A in the same user, the average PPG pulseamplitude is substantially at or near its local maximum value. In thisexample, maximal MSKC pumping of the user consistently occurred duringearly diastole per the step timing markers 44 shown in FIG. 6C.Therefore, in this example, a local maximum average pulse amplitude maybe a reasonable target PPG morphology for guiding a user to MCP,representing a relative preferred value of the measured characteristic(pulse amplitude, in this example) of the signal.

Various methods may be used, alone or in combination, to identify atarget PPG signal characteristic that is indicative of optimal MSKC toCC relative timing. Quantifying metrics that target thesecharacteristics, such as the PPG pulse amplitude as just described, canbe used as part of a feedback loop to provide appropriate guidance to auser. Other examples of characteristics and metrics include beat-to-beatPPG waveform symmetry, peak and valley curvature, and/or signalcomplexity. The analysis may utilize the raw signal or a first or secondderivative of the signals considered in the time domain, or can beconsidered in the frequency domain, wavelet space, or other domain. Inall cases, the purpose is to utilize metrics that, alone or incombination, correlate to the timing relationship between the MSKC andthe CC of the user. Details of such methods will be described more fullythrough the use of examples below.

As shown in FIGS. 6C and 6D, a PPG morphology of a user is sustained atsubstantially maximum average pulse amplitude 46, with FIG. 6Drepresenting a shorter time interval for better visualization ofwaveform morphologies. An accompanying accelerometer signal 48 inrelation to the ECG R-Wave timing indicated by 45 and the calculatedmaximal MSK pump (step) timing 49 are shown in FIGS. 6D and 6E. FIGS. 6Band 6E illustrate a PPG morphology of a user when the PPG waveform 47approaches a local minimum in pulse amplitude, with FIG. 6E representinga shorter time interval. In exemplary systems, as the HR and MSKCfrequency are increasingly different, the beat frequency caused by theoverlapping waves increases and becomes less and less distinct and moreand more difficult to identify clearly. For example, it may becomedifficult to measure a beat frequency of 60 beats per minute, running ata stride frequency of 180 steps per minute, when the HR is only 120beats per minute, because the beats can become increasingly obscured asthe beat frequency continues to rise. Therefore, in some embodiments, aseparate MSKC sensor, such as an accelerometer, for identification of anMSKC signal, as described above, may optionally be utilized to identifythe MSKC frequency of the user during rhythmic physical activity.

To further illustrate the behaviors described above, FIGS. 6F and 6Gshow plots of simultaneously collected ECG 600, PPG 610, andaccelerometer 620 signals of a user walking on a treadmill. To generatethese signals, a PPG sensor was placed on the user's forehead, whilesimultaneous ECG and accelerometer signals were obtained with respectivesensors placed on the users chest. Horizontal line 630 represents theaverage accelerometer signal that is obtained when the user is notmoving (i.e., approximately equivalent to 1 g, the acceleration due togravity). As shown in FIG. 6F, the user's MSK pump timing (step timing),as indicated by the points 640, where the largest upslope during eachMSKC of the accelerometer signal 620 crosses the horizontal line 630,occurs at approximately 40% of the RRI, using R-wave events 24 (FIG. 4B)as the timing marker for the CC. In this example of a relative MSKC toCC timing of 40% of the RRI, the PPG waveform 610 exhibits a morphologycomprising a smooth rounded upper portion and a more-flattened lowerportion, as shown in FIG. 6F.

FIG. 6G illustrates changes in PPG signal 610 when the user steps at anMSKC to CC timing closer to 0% RRI. The waveform shape of signal 610 inFIG. 6G differs from the same signal in FIG. 6F, namely the upperportion is more flattened and the bottom is more rounded. Beyond thepulse amplitude as described above, these resulting morphologicdifferences in the PPG signals 610 in FIGS. 6F and 6G, seen also inFIGS. 6A-6E, may be used by the system to characterize the generaldegree of coordination between the MSKC and CC blood pumps, since thedifferent waveform shapes correlate directly to the actual MSKC to CCtiming relationship of the user. Such characterization of the morphologymay be computed in a variety of ways, as will be described more fullybelow.

FIGS. 6G-F also represent signals from exemplary systems and methodsthat characterize an observed CC timing relationship with respect to anactual CC central blood pump timing of a user as a step in calculating apulse transit time and/or assisting in calibration of the system for aspecific user. For example, a PPG sensor at a specific peripherallocation may be compared to a simultaneous ECG signal of the user inorder to calibrate the system such that the true CC timing can be moreaccurately characterized with a PPG sensor alone after the user is nolonger contacting both ECG leads.

As is illustrated in FIGS. 11 and 12, in some embodiments of the systemand method, the pulse transit time of a sensed arterial pressure wavecan be determined on a processor by comparing an aspect of aplethysmographic signal that repeats at the HR of the user (the CCtiming signal of a plethysmogram) from a peripherally-mounted sensor(e.g., on the wrist or head of a user) to the timing of a simultaneousECG signal. In example embodiments, as shown in FIG. 11, a PPG and/orIPG sensor 1110 in a device mounted on the wrist 1100 may be usedsimultaneously with an ECG sensor also in the same wrist-based system,with a first electrode continuously contacting the wrist of the user1120, and a second electrode 1130 on an externally facing surface of thesame device. The user may complete the ECG circuit 140 by touching afinger of their opposite hand to the second electrode 1130 of thesensor, so that the ECG signal may be measured and an ECG CC timingdetermined on a processor, for comparison to the simultaneously measuredplethysmographic CC signal timing, on the same processor or a differentprocessor.

Alternatively, in another exemplary embodiment as shown in FIG. 12, anear-based device 1200 may include one or more sensors of blood pressure,volume or flow 1210 (e.g. plethysmographic) as well as a pair ofelectrodes, one in contact with the skin of the head or ear of the user1220, and the other insulated from the tissue of the head or ear, butaccessible to the touch of the user's hand 1230, as shown in FIG. 12. Insuch exemplary embodiments, the user may touch the exposed electrode1230 with the skin of a finger, as shown in FIG. 12, for example afinger of the user's left hand when touching a head-based device, inorder to complete the ECG circuit 1240 and measure the ECG and PPGsignals simultaneously for comparison of their CC signals of CC timing.

FIG. 7A illustrates a flow chart for favorably coordinating a timingrelationship between an MSKC of a rhythmic musculoskeletal activity of auser and a CC of the user using a sensor to provide signals thatcorrelate to a cyclically-varying arterial blood volume in a tissue ofthe user, for example, a plethysmography sensor. As shown in FIG. 7A, apreferred method of favorably coordinating a timing relationship betweenan MSKC of a rhythmic musculoskeletal activity of a user and a CC of theuser includes the steps of recurrently providing a movement guidancefrom a prompt device to the user for guiding performance of the rhythmicmusculoskeletal activity S700 a; detecting a signal, using a sensor,that correlates to a cyclically-varying arterial blood volume in atissue of the user S710 a; determining an actual value of a measuredcharacteristic of the signal that varies with the timing relationshipbetween the MSKC and the CC of the user S720 a; computing a trend of theactual value of the measured characteristic using a processor S730 a;and adjusting the movement guidance based on the trend of the actualvalue of the measured characteristic so as to cause the actual value ofthe measured characteristic to approach a relative preferred value ofthe measured characteristic S740 a. This process continues by returningafter step S740 a to step S710 a in a repetitive manner, for example,repeating for a duration of an exercise, or as long as certain exerciseor physiological data are maintained, or for a predetermined period oftime.

In some embodiments, the methods of FIGS. 7A-B may include a calibrationprocess. The calibration process may include the steps of detecting asecond characteristic of the signal or one or more additional signalscorresponding to a physiological metric that varies with the timingrelationship between the MSKC and the CC of the user, using the sensoror one or more additional sensors, and determining the relativepreferred value of the measured characteristic as a relative value ofthe trend that corresponds with a preferred value of the physiologicalmetric. Further examples of such calibration processes are providedbelow in the section titled Calibration Methods. In exemplaryembodiments, the movement guidance comprises an audible, visual, ortactile prompt. In example implementations, the movement guidanceprompts the user in at least one of MSK activity timing and MSK activityeffort. For example, activity timing guidance may provide the prompt tothe user at a prompt rate, such that the HR of the user is substantiallyan integer multiple of the prompt rate, and adjusting the movementguidance means adjusting the prompt rate. In other exemplaryembodiments, adjusting the movement guidance means guiding the user toalter a stride length during running or walking; to change a gear whileriding a bicycle; to change a distance of movement, resistance, orincline using exercise equipment; or to modify a stroke length duringrowing or swimming, in each case in order to modify their effort at agiven MSKC frequency.

In certain embodiments, the relative preferred value is a targetbehavior of the trend of the value of the measured characteristic andfurther adjusting the guidance based on a difference between trend ofthe actual value and the relative preferred value of the measuredcharacteristic guides the user towards substantially obtaining andmaintaining the relative preferred value (“target behavior”) of themeasured characteristic. For example, a target behavior of the trend ofthe value of the measured characteristic of a PPG waveform may includepreferred behaviors such as, for example, at least one of an increasingpulse amplitude, a decreasing waveform complexity, and a change intiming of an aspect of the PPG signal that repeats at a HR of the usertowards a target timing relationship relative to an aspect of an MSKCtiming signal that repeats at an MSKR of the user.

In additional embodiments of the method, the relative preferred valuemay be a target value of the measured characteristic, said target valuecorresponding to the target timing relationship between the MSKC and theCC of the user. For example, a target value of a PPG waveform mayinclude exemplary preferred relative values such as at least one oflocal maximum pulse amplitude, a local minimum waveform complexity, anda target timing relationship of an aspect of the PPG signal that repeatsat a HR of the user relative to an aspect of an MSKC timing signal thatrepeats at an MSKR of the user. FIG. 7B illustrates another flow chartfor favorably coordinating a timing of a rhythmic MSKC with a timing ofa CC of a user using a sensor that provides signals that correlate tothe cyclically-varying arterial blood volume in a tissue of the user,such as, for example, a plethysmography sensor (e.g. PPG or IPG), inaccordance with a preferred embodiment. Exemplary steps include therepetitive cycle of detecting a signal, using a sensor, responsive tocyclically varying blood volume in a tissue of the user S700 b;determining a first measured characteristic of the signal that repeatsat a HR of the user and determining the HR of the user from the firstcharacteristic S710 b; recurrently providing a guidance prompt from aprompt device to the user as a timing indication for performance of arhythmic MSK activity, wherein the HR is an integer multiple of the rateof the timing indication 720 b; determining a value of a second measuredcharacteristic of the signal that varies with an actual MSKC to CCtiming relationship of the user 730 b; and adjusting the guidance basedon a trend of the value of the second measured characteristic towards arelative preferred value of the second measured characteristiccorresponding to a target MSKC to CC timing relationship, therebyguiding the user towards substantially obtaining and maintaining thetarget timing relationship 740 b. After completion of step S740 b, theprocess loops back to S700 b, making the process repetitive, repeating,for example, for a duration of an exercise or a predetermined period oftime.

In an exemplary embodiment, the detected signal S700 b may comprise aPPG signal, and the first measured characteristic that repeats at the HRof the user 710 b may be the peaks of the signal that correspond withsystolic arterial pressure 31 (FIG. 6E). In certain exemplaryembodiments wherein the detected signal S700 b is a PPG signal, thefirst measured characteristic 710 b may be available to correlate to theHR of a user only intermittently, but for adequate durations tocalculate a HR of a user. For example, referring to the beat phenomenonillustrated in FIG. 6A, the first measured characteristic 710 b may bethe regularly occurring peaks of the signal that equal or surpass apredefined or relative amplitude or shape characteristic (such as seenin FIG. 6D, 46), because, for example, the larger and/or sharpersystolic peaks in the PPG may be easier to identify reliably. Anexemplary signal with intermittently oscillating PPG amplitudes isillustrated in FIG. 6A, wherein the relatively larger and easier toidentify systolic peaks 31, magnified in FIG. 6D, may be more accessiblefor reliable interpretation than the relatively smaller and potentiallymore difficult to identify systolic peaks 31 in FIG. 6E.

Alternative embodiments of the method of FIG. 7B may alternatively oradditionally leverage a measured characteristic that is different fromthe first measured characteristic described in step S710 b in order todetermine the HR of the user. For example, if the value of the MSKR isavailable from another sensor (e.g. accelerometer), then the frequencyof the beat phenomenon, as illustrated in FIG. 6A, may be measured fromthe PPG signal and then added to or subtracted from the value of theMSKR in order to obtain the value of the HR. In further embodiments, CCtiming measurements, for example using plethysmography orelectrocardiography, can be improved by measuring signals sensitive tothe MSKC, such as through the use of an accelerometer, and incorporatingthese signal values into a noise cancellation or attenuationmethodology. In further exemplary implementations of FIG. 7B, adjustingthe guidance means adjusting the prompt rate. In yet other exemplaryembodiments, adjusting the guidance includes guiding the user to altereffort at a given MSKC frequency (e.g. alter stride or stroke length ata given MSKC cadence, incline or resistance on an exercise device,etc.).

Referring now to the flowcharts shown in FIGS. 7A and 7B, in someembodiments, the measured characteristic S720 a and second measuredcharacteristic S730 b may include a pulse amplitude of a plethysmographysignal detected in S710 a and S700 b, respectively, as is illustrated bythe exemplary PPG signal in FIG. 6 and as was described above.Alternatively or additionally, in some embodiments, the measuredcharacteristics S720 a and S730 b may include a measure of thecomplexity of the signal from the sensor. The amount of smoothness or“noise” in a waveform relates to the complexity of the signal. Forexample, in certain circumstances, when the CC and MSKC contributions toblood volume in the local tissue at the measurement site are cyclingwith each other constructively, the pulse amplitude is greatest, asshown by waveform 46 in FIGS. 6A and 6D, and the waveform is generallysmooth or substantially sinusoidal, resulting in reduced complexity.Conversely, when the CC and MSKC contributions are out of alignment,there is an appearance of extra features in the waveform (over thetiming of one complete CC) resulting in increased complexity, such asseen by 47 in FIG. 6E.

In further embodiments, the asymmetry of the sensed signal waveforms maybe analyzed with a processor in order to determine additional timinginformation, for example, to determine whether the MSK timing isoccurring slightly early relative to a target timing relationship orslightly late relative to a target timing relationship. Additionally oralternatively, the measured characteristic of the signal may be computedusing a combination of two or more unique characteristics of the signalthat vary with the timing relationship between the MSKC and the CC ofthe user. For example, at least one of the trends in changes of aspectsof the complexity, amplitude, and symmetry of the PPG signal may beidentified and utilized simultaneously in the steps of determining avalue of a second measured characteristic S730 b, as described in FIG.7B, or in computing a trend of the actual value of the measuredcharacteristic on a processor S730 a, as described in FIG. 7B. In onesuch embodiment, target characteristics of a PPG signal on the head of auser may include a target combination of both maximal relative pulseamplitude plus minimal signal complexity. In other embodiments, themeasured characteristic may include the relative phase between the twocontributing signals as computed, for example, using a Fourier transformand retaining the complex term (phase). In yet another exampleembodiment, the characteristic may be a measure of the number ofinflection points of the waveform per cycle of the MSKC or CC. As notedabove with respect to waveforms 610 in FIGS. 6F-G, another measuredcharacteristic that may be considered alone or in combination mayinclude the relative curvature of the PPG peaks and valleys, quantifiedfor example by computing a ratio of the relative amount of change insignal amplitude adjacent to the peak signal to the amount of changeadjacent to the valley, considered over individual cycles in the PPG.

Steps 730 a and 730 b include determining an actual value of themeasured characteristic of the signal that varies with the timingrelationship between the MSKC to CC of the user. The trend may becomputed as the difference in the value observed, or a series of valuesobserved, at two or more different times, such as the most recentlyobserved value and the value available immediately preceding it, oralternatively, the average change over several recent sample periods.Considering the PPG signal 41 of FIG. 6A, the trend of the pulseamplitude can be seen to oscillate approximately seven times over theduration of the graph. In the final seconds of the graph in FIG. 6A, themost recent trend exhibits the behavior of a decreasing pulse amplitude,and a decreasing average pulse amplitude. Steps S740 a and S740 binclude a relative preferred value of the measured characteristiccorresponding to a target relative MSKC to CC timing. The term “relativepreferred value” used in conjunction with FIG. 7 refers to a preferredvalue of the measured characteristic in comparison to the value ofrecent instances of the characteristic, or equivalently, a preferredrelationship of the actual value of the measured characteristic relativeto the trend of the value of the measured characteristic, as isdescribed more fully below. This preferred relationship may correlatewith an MSKC to CC timing relationship consistent with MCP.

In some embodiments, the target MSKC to CC timing may target thecondition of MCP. The value of the measured characteristic correspondingto this condition may depend on the nature of the signals detected inS710 a and S700 b and where on the body the sensor is located. In oneembodiment, the relative preferred value of the measured characteristicduring MCP may correspond to a pulse amplitude of an observedplethysmography signal exhibiting a behavior of reaching its localinstantaneous maximum in its trend over the recent history of theobserved pulse amplitude. Alternatively, the relative preferred valuemay correspond to a local maximum in the average of the pulse amplitudecompared to its recent history. In other embodiments, a local minimum inthe trend of the pulse amplitude may be associated with MCP, or anaverage maximum pulse amplitude minus the average minimum pulseamplitude over a given rolling window of time. Similarly, in yet anotherembodiment, the relative preferred value may correspond to a localminimum complexity in the PPG signal. Alternatively, the relativepreferred value may correspond to a local maximum complexity incomparison to its recent history. In further exemplary embodiments, therelative preferred value may correspond to a maximal local average ofthe absolute values of the derivative of the PPG signal or to a minimallocal average of the absolute values of the second derivatives of thePPG signal. In other embodiments, the trend of the measuredcharacteristic may be used to identify a specific relative value of themeasured characteristic corresponding, for example, to the value of alocal maximum or, in another example, a value of a local minimum in thetrend. The system may then adjust the guidance based on a differencebetween the actual value of the measured characteristic and thispreviously identified specific relative value from the trend. In anotherexample embodiment, the relative value of the measured characteristicmay correspond to a point in the trend when the value changes sign fromnegative to positive, or in a different example, from positive tonegative, crossing a threshold value of zero either in a positive slopeof the trend or a negative slope in the trend, respectively. In someembodiments, the relative preferred value corresponding to a target MSKCto CC timing is determined empirically according to a calibrationprocess, which is described more fully below.

In an exemplary system, the user is provided with a guidance promptcomprising a metronome that repeats at a rate that matches an expectedHR of the user during their rhythmic activity. The user times theirrhythmic activity to occur with the metronome, and as the user's HRapproaches this rate, a PPG signal measured on the user, such as in FIG.6A, begins to exhibit a behavior of a cycling pulse amplitude (pulseamplitude representing the measured characteristic of the signal).Considering a relative preferred value of the measured characteristic tocorrespond to a local maximum in the pulse amplitude, the system mayincrease the period of the metronome when the trend of actual value ofthe measured pulse amplitude stops increasing over time and begins todecrease. If the trend of the pulse amplitude responds to the change inmetronome by increasing, the metronome period continues unchanged. Whenthe pulse amplitude again begins to decrease, having passed its localmaximum, the system decreases the metronome period so as to reverse thetrend in the decreasing pulse amplitude, thereby causing the pulseamplitude to approach the relative preferred value and substantiallymaintain the target timing relationship between the user's MSKC and CC.

In addition to the steps illustrated in FIGS. 7A and 7B, in order toobtain an MSKR, embodiments may include a second signal from a secondsensor responsive to the MSKC of the user, for example, an accelerometersignal 48 from an accelerometer, as shown in FIGS. 6D and 6E, may beused.

In certain embodiments, one of the characteristics of the signal thatcorrelates to a cyclically varying arterial blood volume in a tissue ofthe user may be a timing of a recurrent aspect of the signal that varieswith the HR of the user, which may be used alone or in combination withexemplary measured characteristics of the signal previously described.For example, relatively high pulse amplitude may be one preferredmeasured characteristic of a PPG signal in a tissue on the head of auser indicating that the MSKC to CC timing relationship is approaching apreferred MSKC to CC timing relationship. In this example, pulse peaktiming at the higher pulse amplitude may be an aspect of the signal thatcorrelates with a CC timing, such that the timing of the CC can therebybe compared to the timing of the MSKC detected from a second sensor(e.g. accelerometer), and these signal timings can be used to determineboth a measured and an actual MSKC to CC timing relationship using aprocessor, wherein, for example, the actual timing relationship iscorrected for pulse transit time. The timing indication of the promptmay then be adjusted, as indicated, based on a difference between theactual timing relationship and the preferred timing relationship, so asto reduce the magnitude of the difference.

In some embodiments, the method of FIGS. 7A and 7B may further includeproviding MSK activity guidance or adjusting MSK activity guidance onlywhen the absolute value of a difference between the musculoskeletalactivity cycle rate (MSKR) and HR is less than, or less than or equalto, the specified allowable difference.

Exercise Systems and/or Technologies for Favorably Coordinating CC andMSKC Timing

Now turning to exemplary exercise equipment systems for implementingsystems and methods of FIGS. 1-7. FIG. 8 illustrates a treadmill systemfor sensing a CC and MSKC timing of a user and guiding a user to thetarget MSKC to CC timing relationship, in accordance with a preferredembodiment. A treadmill system, as shown in FIG. 8, may be used todetermine a target MSKC to CC timing relationship, as well as to guide auser to the target MSKC to CC timing relationship. As shown in FIG. 8,the treadmill system 800 may include a user input interface 801, aprocessor/controller 810, an exercise equipment interface 816, a userguidance interface 820, a motor driver 813, an incline driver 818, and atrack 822 on which the user 808 may run or walk. The treadmill system800 may include a chest strap 809 for measuring the CC of the user 808with CC sensor 812. Alternatively, any type of wearable sensor or devicemay be worn by the user to measure a CC of the user, for example a smartwatch and/or a chest strap 809 with HR and/or MSKC sensor. The MSKC ofthe user may be measured in one embodiment by using sensor 811 included,for example, within chest strap 809, or in another embodiment as acomponent of the treadmill such as load cell 814 or an accelerometer. Inyet another embodiment, a single sensor, combining the function ofsensors 811 and 812, may be used for sensing both the CC and MSKC of theuser or, for example a PPG sensor, as was described more fully above.The functioning and embodiments of the user input interface 801, CCsignal sensor 812, MSKC sensor 811 or 814, processor 810, and exerciseequipment interface 816 were described above in connection with FIGS. 1and 2.

As shown in FIG. 8, an MSKC sensor 814, for example a load sensor, maybe used to sense the load of the user 808 as a foot of the user strikesthe track 822 of the treadmill 804. In some embodiments, the informationcollected by the MSKC sensor and CC sensor may be transmitted to theprocessor for determining the actual and target MSKC to CC timingrelationships, as described above. Sensor 814 represents one example ofa location and type of MSKC sensor that can be used with the exerciseequipment. In addition to the body-worn MSKC sensors describedpreviously, other examples of MSKC sensors on the equipment includevibration, switch, optical, video, and pressure sensors, or any otherswell known in the exercise equipment industry. In further embodiments, acomputer, for example, a tablet computer, may be placed on or attachedto the exercise equipment, said computer including or communicating withat least one of an MSKC sensor (e.g. accelerometer or user facingcamera) and a CC sensor (e.g. user facing camera).

Also as shown in FIG. 8, an exercise equipment interface 816, user inputinterface 801, or user guidance interface 820 may be used by a user orautomatically controlled by the processor 810 to adjust the motor driver813 to increase or decrease speed and the incline driver 818 to raise orlower the incline of track 822. Further, additional sensors may be usedto detect hand gestures or other body movements that are recognized ascommands for adjusting the treadmill incline, treadmill speed, type ofmusic, playlist selection, volume control, type of graphical display,graphical display selection, or any other type of controls. In someembodiments, one or more automation features may be used to guide a usertowards a target MSKC to CC timing relationship, for example using theuser guidance interface 820. Alternatively, a user may abort anautomatic setting or turn off an automatic setting to enable manualcontrol of the motor driver 813 and incline driver 818 or any otherfeature of the treadmill.

In some embodiments, exercise equipment interface 816, user inputinterface 801, or user guidance interface 820 may also provide visualdisplays of information, such as raw data, processed data, or acombination thereof. For example, a HR, ECG, EEG, estimations of fat orsugar metabolism, blood insulin concentration, blood glucoseconcentration, step rate, MCP of the arms and/or legs, tissue lactateconcentration, watts per beat, meters per beat, distance, and heelstrike of a user may be displayed on the interface 801, 816, 820. Insome embodiments, user guidance interface 820 may be used to provideguidance to the user. Guidance may be provided in an audible cue, visualdisplay, tactile feedback, or other features that alert the user to achange in guidance, for example to increase or decrease stride length;to guide the user towards stepping every 2 beats, 3 beats, or 4 beats;or to coach the user to improve MSKC timing, concentration, or effort.As described above, reaching a target MSKC to CC timing relationship andother desired physical states, including desired HRs and MSK activitylevels may be accomplished with treadmill system 800.

FIG. 9 illustrates a biking system 900 including an exercise equipmentinterface, user input interface, or user guidance interface 907 forsensing a CC and MSKC timing of a user 908 and guiding the user to atarget MSKC to CC timing relationship, in accordance with an alternativepreferred embodiment. As show in FIG. 9, one or more sensors may beintegrated with one or more components of a bike, such as a pedal, tire,crank, hub, spoke, derailleur, or bike chain to obtain measurements ofspeed, distance, acceleration, power, etc., and to determinerelationships with other physiological metrics. As shown in FIG. 9, astationary bike may include a sensor 902 on the back frame tube 904, asensor 910 on a second frame tube 909, a sensor on the pedal 905, afirst foot sensor on the first pedal crank 906, and a second foot sensor(not shown) on the second pedal crank. One or more of the bike sensorsas described above may be used to identify an actual or a preferred MSKCtiming. For example, each revolution of the pedal may equal one MSKC, ormay equal two, including one MSKC for each leg. In some embodiments, thesignals from the one or more MSKC sensors on the bike may be compared tothe timing of signals from at least one sensor worn by the user, forexample a chest strap sensor 911 to sense a CC of the user 908.Comparison of a body worn ECG based CC sensor to an exercise equipmentbased CC sensor may be useful in calibration of embodiments of thesystem. Alternatively, a chest patch sensor, an implanted sensor, awrist-based sensor, a head-based sensor, or another device previouslydescribed above may be worn by the user to measure a CC and/or MSKC ofthe user. Thus, for example, body versus pedal MSKC timing informationmay be determined and synchronized according to embodiments of exerciseequipment as described herein. In some embodiments, synchronizing bodyversus pedal MSKC timing may require a characterization step, as will bedescribed below. Alternatively, a sensed body movement metric may bedetermined and synchronized in order to calibrate the system MSKC pumptiming. In some embodiments, synchronization or characterization ofclocks on sensors, may be done using one or more accelerometers.Synchronization and characterization may require the user to performcoordinated actions that register distinguishable events in the dataprovided by the sensors, such that the distinguishable events may beused for correlating internal clocks of the sensors.

For a non-stationary or stationary bike, as shown in FIG. 9, exemplaryembodiments of characterization algorithms include use of a body versusbody MSKC sensor timing comparison. Further embodiments include a bodyMSKC sensor versus bike MSKC sensor timing comparison, each having aninternal clock. In some embodiments, syncing the two clocksintermittently may be performed to characterize or checkcharacterization at periodic events such as on the occasion that theuser stands up on the pedals during MSKC. For example, thischaracterization maneuver may be a required step every few minutesduring the use of the system. The characterization maneuver mayincorporate two identical chip and accelerometer configurations (e.g.chest strap and bike crank) to correct for clock drift.

Calibration Methods

FIG. 10 illustrates a flow chart for determining a target MSKC to CCtiming relationship empirically, i.e., “calibrating” a system, inaccordance with a preferred embodiment. As shown in FIG. 10, a methodfor determining a target MSKC to CC timing relationship of a preferredembodiment includes detecting a first characteristic of a signalresponsive to a CC timing of a user that repeats at a frequency thatcorresponds to the HR of the user using a sensor S1000; detecting asecond characteristic of a signal responsive to a rhythmic MSK activitytiming of the user that repeats at a frequency that corresponds to theMSKR of the user using a sensor S1010; determining a valuerepresentative of an actual timing relationship between the firstcharacteristic and the second characteristic S1020; detecting a thirdcharacteristic of a signal using a sensor corresponding to aphysiological metric that varies with the actual timing relationshipS1030; and determining the target value representative of a preferredtiming relationship between the first and second characteristics byidentifying the value representative of the actual timing relationshipthat corresponds with a preferred value of the variable physiologicalmetric S1040.

The method preferably functions to calibrate or recalibrate the systemempirically so that the system may be tailored to each user, activity,device configuration, and/or time. For example, the relationship betweenMSKC timing and CC timing that leads to a preferred value of aphysiologic variable may vary among users engaged in a similar physicalactivity, between different activities for one user, and/or betweendifferent instances of the same activity over time. Additionally, thespecific system configuration can affect the measured relative timing.For example, use of the ECG T-wave vs. the R-wave vs. the peak systolicamplitude of a PPG signal as a timing indication impacts the measured CCtiming, as does the location of the PPG sensor. Additionally, thelocation of a crank sensor placed on a bicycle and the location of theMSKC sensor incorporated within a treadmill system impacts the valuesand timing of the signals used to measure MSKC timing independent of theunderlying timing of the CC and MSKC blood pumps. Thus, the method asshown in FIG. 10 functions to calibrate or recalibrate the systemempirically to correct for or plan for any of the factors that canaffect the measured MSKC to CC timing relationship and its relationshipto a target physiological condition (e.g., MCP) or a preferred value ofa physiologic variable (e.g., a reduced HR).

In some embodiments, a system may be configured to determine the optimalrelative MSKC to CC timing of a user once. Alternatively, the system maytemporarily switch back to a “calibration mode” periodically to ensureongoing optimization of timing. In both cases, in an example embodiment,a HR of a user while exercising at a given work load may correlate withthe timing of the MSKC relative to that of the CC, with relatively lowerHR values at a given work load associated with improved overall bloodpump hemodynamics. By exposing the user to a variety of relative MSKC toCC timing values over a period of time, and then identifying therelative timing value, characteristic, or relative value relationshipassociated with the lowest HR, the system may be used to identify the“favorable” or “optimal” timing relationship and/or hemodynamic sensorsignal characteristics for the specific user, activity, and systemconfiguration in use during the calibration process. This empiricallydetermined value, signal characteristic, or relative value relationshipmay then be used subsequently to represent the target MSKC to CC timingrelationship. Optimal timing relationships may also be derived fromadditional or alternative measures other than HR.

As shown in FIG. 10, step S1000 includes detecting, using a sensor, afirst characteristic of a signal responsive to a CC timing of a userthat repeats at a frequency that corresponds to the HR of the user. StepS1000 may, in example embodiments, function to identify a recurrentaspect of a CC of the user, as described above. In some embodiments, thefirst characteristic may be one aspect of a signal, for example from ECGor PPG, such that other aspects may be used to define othercharacteristics, for example an MSKR.

As shown in FIG. 10, step S1010 includes detecting a secondcharacteristic of a signal responsive to rhythmic MSKC timing of theuser that repeats at a frequency that corresponds to the MSKR of theuser using a sensor. Step S1010 may, in example embodiments, function todetermine a recurrent aspect of an MSKC of a user, as described above.In some embodiments, the sensor in S1000 and S1010 may be the samesensor, for example a PPG sensor. Alternatively, the sensors in S1000and S1010 may include distinct sensors, for example an ECG and anaccelerometer or a PPG and an accelerometer. In some embodiments, thefirst characteristic and the second characteristic are the same aspectof a first signal from a first sensor. Alternatively, the firstcharacteristic and the second characteristic may be different aspects ofa first signal from the first sensor. For example, one or more featuresof a PPG signal may be used to determine a CC and MSKC timing or timingrelationship of a user, as described above in accordance with FIGS. 6and 7. In some embodiments, the first characteristic and secondcharacteristic may be derived from independent first and second signalsfrom first and second sensors, respectively.

As shown in FIG. 10, step S1020 includes determining a valuerepresentative of an actual timing relationship between the firstcharacteristic and the second characteristic. Step 1020 may function todetermine a timing relationship between a CC and MSKC of a user usingthe observed individual timings of the first and second characteristicsof steps S1000 and S1010, respectively. In alternative embodiments, theactual timing relationship may be determined by using a crosscorrelation between the first characteristic and the secondcharacteristic.

As shown in FIG. 10, step S1030 includes detecting a thirdcharacteristic using a sensor corresponding to a physiological metricthat varies with the actual timing relationship. Step S1030 preferablyfunctions to further measure a third physiological parameter of a useras compared to the first and second characteristics. Example physiologicmetrics include, but are not limited to the user's HR, systolic and/ordiastolic blood pressure, cardiac output, cardiac perfusion, muscleperfusion, muscle pH, cerebral perfusion, EEG activity, respiratorygases (e.g., VO2, VCO2, RER), tissue or blood glucose and lactatelevels, and blood insulin levels. In each case, the correspondingpreferred value of the metric reflects a desired condition, generallyassociated with a relatively improved physiologic economy, typically anappropriate minimum or maximum of the respective measure of interest.

Further, the sensors in S1000, S1010, and S1030 may be the same sensorin certain embodiments, or can use two or more different sensors inother embodiments, for example S1000 may be an ECG, while S1010 may bean accelerometer, while S1030 may be a metabolic measurement system forcalculating oxygen consumption, CO₂ production, respiratory volumes, andother related measurements. In an alternative embodiment, the sensor ofS1010, S1010, and S1030 can all represent one or more PPG sensors.

In some embodiments, the system may guide the user towards a target orpreferred value of a physiological metric, such that the physiologicalmetric is at a beneficial or advantageous level to the user.Additionally, the third characteristic may be used to determine when auser achieves MCP or a target MSKC to CC timing relationship. In someembodiments, the first characteristic and the third characteristic maybe the same aspect of a first signal from a first or third sensor.Alternatively, the first characteristic and the third characteristic maybe different aspects of a first signal from the first or third sensor.Alternatively, the first, second, and third characteristics may be threedistinct aspects of a first signal from the first sensor. In someembodiments, the first, second or third characteristics may include aFourier transform.

As shown in FIG. 10, step S1040 includes determining the target valuerepresentative of a preferred timing relationship between the first andsecond characteristics by identifying the value representative of theactual timing relationship between the first and second characteristicsthat corresponds with a preferred value of the variable physiologicalmetric. An exemplary “value” may, for example, include a specific orrelative characteristic or set of characteristics of the signal orsignals described in FIG. 10. Step S1040 may function to identify avalue of the MSKC to CC timing relationship that causes thephysiological metric to exhibit a generally more favorable or preferredvalue, using that identified value subsequently as representative of thetarget timing relationship. For example, a preferred value of aphysiological metric may be a lowest average HR of the user observedunder otherwise constant conditions, because the hemodynamics thatresult from MCP can lead to an average lowest HR for the user. The valuerepresentative of the target MSKC to CC timing relationship (i.e. thevalue representative of the preferred timing relationship between thefirst and second characteristics) might alternatively include, forexample, values described by a sensed PPG signal that correlate with aparticular “PPG shape”, “PPG characteristic” or “PPG relative shape”without knowing exactly the timing relationship represented by thatshape.

In one exemplary process that utilizes the method outlined in FIG. 10for determining a target timing relationship, a user is provided timingprompts for performing a rhythmic activity at a generally stable workoutput level using, for example a treadmill such as shown in FIG. 8 andthe prompting system shown in FIG. 3A. The system is configured to varythe targeted MSKC to CC timing relationship over time to expose the userto a number (at least two) of different timing relationships, and thenidentifies the “optimum” timing relationship that corresponds to arelatively favorable value in the measured physiologic metric. Thisoptimum timing relationship may then be considered the “calibrated”target timing relationship for subsequent use. In an alternativeembodiment, this procedure may be used to identify a measuredcharacteristic of a signal responsive to the actual MSKC to CC timingrelationship that corresponds to the relatively favorable value in themeasured physiologic metric. In one example, the signal may be a PPG andthe measured characteristic may be the pulse amplitude or, additionallyor alternatively, a measure of the signal complexity.

In some embodiments, the method of FIG. 10 may further include providingto the user a recurrent prompt from a prompt device at a prompt rate asa timing indication for performance of the rhythmic musculoskeletalactivity, such that the user's MSKC timing in response to the promptsubstantially correlates with a preferred value of the physiologicalmetric.

In some embodiments, the calibration method of FIG. 10 may be used todetermine a target value representative of a preferred MSKC to CCrelative timing relationship through analysis for trends in sensed MSKCto CC timing signals that occur when a user is guided by an exemplarysystem to readily achieve cardiolocomotor synchronization, therebydetermining signal characteristics that correlate with a naturallypreferred MSKC to CC relative timing relationship.

Natural cardiolocomotor synchronization may be described as“physiological MSKC to CC timing stickiness”—wherein a particular MSKCto CC timing relationship naturally preferentially occurs with thehighest frequency of all possible timing relationships, due to a naturalphysiological tendency for many individuals towards a pump timingconsistent with MCP. Physiological MSKC to CC timing stickiness mayoccur when the HR of the user approaches an integer multiple of the MSKRof a user. Therefore, in embodiments of the system and methods, a useris paced at a MSKR while being guided to a level of exertion at whichthe HR of the user approximates an integer multiple of the MSKR of theuser. With the HR and MSKR substantially aligned in this manner, valuesrepresentative of the MSKC to CC timing relationship are monitored andanalyzed on a processor in order to identify statistically more commonvalues representative of specific CC timing to MSKC timing that may bepreferred, due to the natural tendency for physiology to trend towards ahigher incidence of the physiologically more beneficial (preferred)timing relationships (e.g. timing that is consistent with MCP) and totrend away from timing relationships that are not physiologicallypreferable (e.g. timing that is consistent with iMCP). In anotherexample, the system may be calibrated by monitoring the frequency ofMSKC to CC timing relationships during periods of physical activitywherein the HR approaches an integer multiple of the MSKC without theuser being guided. For example, certain individuals are able tonaturally step with the timing of maximal MSKC arterial pumpingoccurring during early cardiac diastole while running and/or walkingwithout being prompted to do so, at least for statistically significantalbeit often short periods of time. In preferred embodiments of acalibration method, this stickiness is facilitated when users areprovided with an MSKC timing indicator (e.g. a metronome or musical steptiming prompt while running) that is constant while they are guided, toa target HR where the target HR is substantially an integer multiple ofthe MSKR.

In another example method for determining “stickiness”, prompting a userat a rate that is slightly different than an integer multiple of the HRmay be used. For example guiding the user to an MSKR (MSKCs per minute)equal to their current HR plus 1, 1.5, 2, 3, 4 or minus 1, 1.5, 2, 3, 4per minute, may increase the likelihood of seeing the stickinessphenomenon occur over and over as the user sequentially cycles throughvarious MSKC to CC timing relationships. The MSKC to CC timingrelationship stickiness, which may be caused by a naturally occurringneural feedback loop within the cardiac tissue, typically includes anatural physiological delay that may be compensated for on a processorin calibration embodiments of the method and system. In some calibrationembodiments, the system may oscillate or alter MSKC prompt timing inrelationship to the user's CC timing so that the prompt guides the userback and forth across a desired MSKC to CC phase range, while the systemanalyzes the values of the signals for trends consistent with thisphysiological stickiness phenomenon. Further, the system or user mayloosen the “control” in a target MSKC to CC timing relationship range inorder to promote physiological stickiness. For example, automaticcontrols may automatically adjust an incline, speed, cadence, phase, ortarget HR, to bring the MSKR and HR of the user into adequate alignmentto facilitate determination of the values of the sensed signals thatrepresent the most frequent MSKC to CC relative timing of aphysiological timing stickiness of the user.

Some embodiments of the system calibrate the system throughidentification of physiological MSKC to CC timing stickiness, while inother embodiments, one or more of the described techniques of enablingphysiological stickiness may be used as a technique for guiding a userto achieve MCP. In exemplary calibration and MCP guidance embodiments,the user's work output is guided or otherwise directed towards a targetHR, such that the target HR of the user equals an integer multiple ofthe MSKR of the user. The MSKR (cadence) of the user may be an unguided(e.g. naturally occurring) cadence, or the user may be guided by anembodiment of the system to a designated substantially constant cadence,the cadence, in either case, tied to a target HR chosen by the user orsuggested by the system. In some embodiments, the work output may bemodified to approach the target HR. For example, the work output may bemodified by guiding the user to changes in stride length or inclineduring walking or running, or by altering resistance of a bicycle oraerobic exercise machine. Further, the MSK cadence may be determined bythe target HR. Alternatively, the target HR may be determined by thedesired cadence. In some embodiments, a combination of both desiredtarget HR and desired cadence may be used to select an intermediatecadence and target HR.

In another embodiment of a calibration process, the user is providedwith a prompt that guides the user to an MSKR that slightly differs by aconstant amount from the user's HR (e.g., +1 or +1.5 or +2 or . . . perminute) so that the user's MSKC to CC timing relationship cycles, suchas is seen in FIG. 6A. During this period of time (e.g., 1 to 5minutes), the actual timing relationship S1020 and associated values ofthe physiologic metric S1030 are recorded. The target timingrelationship is then determined according to S1040. In yet anotherembodiment, this process is repeated after altering the prompt to guidethe user to an MSKR with an opposite constant difference to their HR(e.g., −1 or −1.5 or −2 or . . . per minute, or vice versa if the formerguidance was to be slower). The final target timing relationship is thendetermined using the two results obtained in S1040 under the twoconditions, for example the average of the two obtained target values,thus helping to compensate for time lag between the observation of thepreferred value of the physiologic metric and the user's actual MSKC toCC timing relationship that enabled it.

In some embodiments, a user may prefer to be alerted when a HR andcadence (MSKR) of the user are nearly aligned, such that the user mayturn on and readily engage in an MCP enabling guidance. Thisfunctionality could also be turned on automatically when MSKR is veryclose to an integer multiple of the HR of a user. Thus, the user may“step to the beat” or “move to the beat” only when the user's cadenceand HR are already nearly aligned. In an exemplary embodiment, a PPGsensor and an accelerometer can both exist in an earbud embodiment ofthe invention. In this exemplary embodiment, the user could be walkingdown the street without thinking about stepping to the beat, when thedevice identifies that the HR and step rate are substantiallyequivalent, therefore notifies the user that stepping to the beat toachieve MCP functionality is easily available. The user may then “optin” at any time, turning on guidance, for example music. In thisexample, the music may be selected from the user's music files for it'sbeat frequency but the beat frequency and timing may be modified, asneeded, so that the beat of the music provides a timing indication thatguides the user to MCP, according to the methods described above.

Embodiments described, and hence the scope of the descriptions ofsystems and methods below, encompass embodiments in hardware, software,firmware, or a combination thereof. It will also be appreciated that themethods, in the form of instructions having a sequence, syntax, andcontent, of the present disclosure may be stored on (or equivalently,in) any of a wide variety of computer-readable media such as magneticmedia, optical media, magneto-optical media, electronic media (e.g.,solid state ROM or RAM), etc., the form of which media not limiting thescope of the present disclosure. A computer reading said media isoperable to either transfer (e.g., download) said instructions theretoand then operate on those instructions, or cause said instructions to beread from the media and operate in response thereto. Furthermore,devices (e.g., a reader) for accessing the instructions on said mediamay be contained within or connected directly to the computer on whichthose instructions operate, or may be connected via a network or othercommunication pathway to said computer.

Furthermore, while a plurality of exemplary embodiments have beenpresented in the foregoing detailed description, it should be understoodthat a vast number of variations exist, and these exemplary embodimentsare merely representative examples, and are not intended to limit thescope, applicability or configuration of the disclosure in any way.Various of the above-disclosed and other features and functions, oralternative thereof, may be desirably combined into many other differentsystems or applications. Various presently unforeseen or unanticipatedalternatives, modifications variations, or improvements therein orthereon may be subsequently made by those skilled in the art which arealso intended to be encompassed by the present disclosure.

In addition, the methods and systems described herein guide the user inthe performance of two major categories of rhythmic physical activities,namely MSK movement and skeletal muscle contraction cycles, in order tofavorably coordinate peripheral vascular pumping with the heart'spumping activity. These two categories of rhythmic physical activities,together or individually, are included in the scope of the disclosure,even where only one of the two categories has been described. Therefore,for example, the descriptive phrases MSK movement, skeletal musclecontraction, skeletal muscle relaxation, MSK pumping cycles, and MSKactivity should in many cases be considered included where one or moreof the terms was not mentioned.

Therefore, the foregoing description provides those of ordinary skill inthe art with a convenient guide for implementation of the disclosure,and contemplates that various changes in the functions and arrangementsof the described embodiments may be made without departing from thespirit and scope of the disclosure.

What is claimed is:
 1. A method for guiding a user towards a targetrhythmic musculoskeletal activity cycle (MSKC) to cardiac cycle (CC)timing relationship, comprising: providing a recurrent prompt from aprompt device to a user, wherein the recurrent prompt is provided toguide the user to time performance of a rhythmic musculoskeletalactivity with the recurrent prompt; detecting a first signal responsiveto the CC of the user using a first sensor; determining, with aprocessor, a CC rate of the user from the first signal; detecting asecond signal responsive to the MSKC of the user using the first sensoror a second sensor; identifying, with a processor, a target MSKC-to-CCtiming relationship; determining, with a processor, an actual MSKC-to-CCtiming relationship between the CC and the MSKC; comparing, with aprocessor, the actual MSKC-to-CC timing relationship to the targetMSKC-to-CC timing; and adjusting the recurrent prompt based on adifference between the actual MSKC-to-CC timing relationship and thetarget MSKC-to-CC timing relationship so as to guide the user to reducethe magnitude of the difference.
 2. The method of claim 1, whereinidentifying a target MSKC-to-CC timing relationship is selected from agroup consisting of: calculating a target MSKC-to-CC timingrelationship, obtaining a target MSKC-to-CC timing relationship from atable, and identifying a pre-programmed value.
 3. The method of claim 2,wherein calculating a target MSKC-to-CC timing relationship at leastpartially comprises one or more of: using a pre-programmed algorithm ortable that utilizes at least one measurement of the physiology of theuser, using a pre-programmed algorithm or table that references a heartrate of the user, using a pre-programmed algorithm or table thatreferences information obtained from an ECG signal of the user, using aprior calibration of an optical target timing of the user, and using apre-programmed algorithm or table responsive to the sex of the user. 4.The method of claim 1, wherein adjusting the recurrent prompt comprisesone or more of adjusting a rate of the recurrent prompt, adjusting atiming of the recurrent prompt, and adjusting a sound of the recurrentprompt.
 5. The method of claim 4, wherein adjusting the sound of therecurrent prompt comprises one or more of changing a: volume, pitch, orone or more musical attributes of the recurrent prompt.
 6. The method ofclaim 1, wherein providing the recurrent prompt from the prompt deviceto a user comprises playing a song having a recurrent beat.
 7. Themethod of claim 6, wherein adjusting the recurrent prompt comprisesautomatically selecting a new song from a playlist, wherein the new songhas a preferred beat frequency that is closer to the beat frequency ofthe sensed MSKC frequency.
 8. The method of claim 6, wherein adjustingthe recurrent prompt comprises adjusting a playback speed of the song tofine-tune timing of the recurrent beat.
 9. The method of claim 6,wherein adjusting the recurrent prompt comprises one or more of changinga volume of the recurrent beat in the song relative to a remainder ofthe song, changing the pitch of the recurrent beat, and changing themusical quality of the recurrent beat within the song in response to achange in an accuracy or consistency of achieving the target MSKC-to-CCtiming relationship.
 10. The method of claim 6, wherein adjusting therecurrent prompt comprises one or more of: changing a volume of anadditional recurrent beat on top of the song relative to a remainder ofthe song, changing the pitch of the additional recurrent beat, andchanging the musical quality of the additional recurrent beat within thesong in response to a change in an accuracy or consistency of achievingthe target MSKC-to-CC timing relationship.
 11. The method of claim 1,wherein the steps of: identifying the target MSKC-to-CC timingrelationship, determining the actual MSKC-to-CC timing relationshipbetween the CC and the MSKC, and comparing the actual MSKC-to-CC timingrelationship to the target MSKC-to-CC timing, are performed by a singleprocessor or by a plurality of processors.
 12. The method of claim 1,wherein adjusting the recurrent prompt comprises adjusting a prompt rateof the recurrent prompt such that the CC rate is an integer multiple ofthe prompt rate.
 13. The method of claim 1, wherein determining the CCrate of the user from the first signal comprises identifying one or motefeatures of the first signal that repeat once per CC, and identifying arate at which the one or more features repeat, wherein the one or morefeatures correspond to one or more of: an ECG R-wave, an ECG T-wave, anend of the ECG T-wave, a peak of a cardiovascular systolic pressure, anadir of a diastolic cardiovascular pressure, and a transition point ina cardiovascular pressure of the user.
 14. A system for guiding a usertowards a target rhythmic musculoskeletal activity cycle (MSKC) tocardiac cycle (CC) timing relationship, comprising: a user guidanceinterface configured to provide a recurrent prompt to a user, whereinthe recurrent prompt is provided to guide the user to time performanceof a rhythmic musculoskeletal activity with the recurrent prompt; afirst sensor configured to sense a first signal responsive to the CC; asecond sensor configured to sense a second signal responsive to the MSKCof the user; and at least one processor communicatively coupled to thefirst sensor, the second sensor, and the user guidance interface, the atleast one processor configured to: receive the first signal from thefirst sensor; receive the second signal from the second sensor;determine a CC rate of the user from the first signal; identify a targetMSKC-to-CC timing relationship; determine an actual MSKC-to-CC timingrelationship between the CC and the MSKC; compare the actual MS KC-to-CCtiming relationship to the target MSKC-to-CC timing; and command theuser guidance interface to adjust the recurrent prompt based on adifference between the actual MSKC-to-CC timing relationship and thetarget MSKC-to-CC timing relationship so as to guide the user to reducethe magnitude of the difference.
 15. The system of claim 14, wherein thefirst sensor signal comprises at least one of an electrocardiogram (ECG)and a plethysmogram.
 16. The system of claim 14, wherein the firstsensor is positionable on an arm, on a finger, around an ear lobe, in anear canal, on a forehead, or over an eye.
 17. The system of claim 14,wherein the second sensor comprises at least one of an accelerometer, anelectromyographic sensor, a pressure sensor, a switch, a camera, agryroscope, a proximity sensor, and a plethysmographic sensor.
 18. Thesystem of claim 14, wherein the user guidance interface is configured toplay music to the user.
 19. The system of claim 18, wherein therecurrent prompt is an audible prompt that comprises a beat of a musicaltrack.
 20. The system of claim 19, wherein a volume of the beatcomprising the recurrent prompt is controlled separately from a volumeof a remainder of the musical track based on at least one of a usersetup configuration, a program setup configuration, a consistency of theuser in stepping to the recurrent prompt, or an accuracy of the userstepping with the recurrent prompt.
 21. The system of claim 14, whereinthe at least one processor comprises a plurality of processors, andwherein each of the plurality of processors is configured to perform oneor more functions.
 22. The system of claim 14, wherein some of or allthe system is wearable and positioned on or in one or more of a: cheststrap, helmet, headband, hat, visor, sports bra, watch, wristband,armband, ankle band, headset, earbud, glasses, goggles, or patch.